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Association of Interleukin-10 Genotypes and Oral Cancer Susceptibility in Selected Malaysian Population: A Case- Control Study

Goud EVSS, Malleedi S, Ramanathan A, Wong GR, Hwei Ern BT, Yean GY, et al.

Asian Pac J Cancer Prev, 2019 Mar 26;20(3):935-941.
PMID: 30912418

Background: Interleukin-10 (IL10) genotypes have been closely correlated to the susceptibility for oral squamous cell
carcinoma. More than half of oral cancers in the world occur in Asia with estimated 168,850 new cases were diagnosed
in this geographical region alone. Considering the rising numbers of oral cancer cases in Malaysia, association of IL10
A1082G gene polymorphism was correlated. Methodology: 41 oral squamous cell carcinoma (OSCC) cases and 48
healthy controls of comparable age, gender, and with habits like smoking, alcohol consumption and betel quid chewing
were selected. In this case-control study, samples were collected from the Oral Cancer Research and Coordinating
Centre (OCRCC), Faculty of Dentistry, University of Malaya, Malaysia. Genotyping conditions were evaluated by
polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The PCR products were subjected
to digestion by MnlI enzyme (NEB, UK) to screen for the IL10 A-1082G. Digested DNA products were analyzed by
electrophoresis on 4% (w/v) agarose gel, stained with ethidium bromide and imaged under UV illumination. Chi-square
test and Fisher’s Exact test were used in statistical analysis. Results: AG genotypes were present in 81.3% and 86.0% of
healthy control and OSCC cases respectively (OR=0.468, 95% CI=0.133-1.653). No significant association was found
between IL10 A1082G polymorphism with risk habits, clinico-pathological parameters and 5-years overall survival.
The findings also show no significant correlation between the IL10 genotype and features of OSCC within the case
group as measured by tumor size, lymph node involvement, stage, invasive front, grading, depth, pattern of invasion.
Conclusion: This study suggests that functional polymorphism AG of IL10 A1082G may have no influence with OSCC
susceptibility. However, further investigation with larger sample sizes can be conducted to provide additional evidence
to support the lack of association of IL10 A1082G polymorphism in oral cancer.

Matched MeSH terms: Carcinoma, Squamous Cell/secondary
Wire guided localisation for targeted axillary node dissection is accurate in axillary staging in node positive breast cancer following neoadjuvant chemotherapy

Balasubramanian R, Morgan C, Shaari E, Kovacs T, Pinder SE, Hamed H, et al.

Eur J Surg Oncol, 2020 06;46(6):1028-1033.
PMID: 31879050 DOI: 10.1016/j.ejso.2019.12.007

AIM: This study investigated whether wire localisation of the histologically proven positive, clipped axillary lymph node (ALN) with subsequent targeted axillary dissection (TAD) following neoadjuvant chemotherapy (NACT) improves axillary staging in breast cancer.
MATERIALS AND METHODS: We performed a retrospective review of patients with primary breast cancer and core biopsy proven metastatic ALNs, that had an excellent nodal radiological response following NACT, treated at our centre between January 2016 and December 2018. The initial cohort of patients (Group 1) underwent sentinel lymph node biopsy (SLNB), with a minimum of three nodes were sampled. The subsequent cohort (Group 2) had a marker clip inserted in the metastatic ALN prior to NACT. This cohort underwent wire guided excision of the clipped node in addition to SLNB, with a minimum of three nodes sampled.
RESULTS: A total of 47 patients were identified. Group 1 comprised 22 patients with a sentinel lymph node (SLN) identification rate (IR) of 95%. 25 patients (Group 2) underwent wire guided clip location and the SLN IR was 100% with a 92% clipped node IR. Evidence of pathological complete response (pCR) in the clipped node was associated with pCR in other nodes.
CONCLUSION: Targeted axillary dissection is a feasible technique following excellent response to NACT in selected patients with limited volume ALN metastasis, at diagnosis. The identification of the positive ALN during surgery is vital and the IR can be improved by clipping the node prior to NACT and wire guided localisation at the time of surgery.

Matched MeSH terms: Breast Neoplasms/secondary
Fulltext Low miR-19b-1-5p Expression Is Related to Aspirin Resistance and Major Adverse Cardio- Cerebrovascular Events in Patients With Acute Coronary Syndrome

Singh S, de Ronde MWJ, Creemers EE, Van der Made I, Meijering R, Chan MY, et al.

J Am Heart Assoc, 2021 01 19;10(2):e017120.
PMID: 33441016 DOI: 10.1161/JAHA.120.017120

Background Because of a nonresponse to aspirin (aspirin resistance), patients with acute coronary syndrome (ACS) are at increased risk of developing recurrent event. The in vitro platelet function tests have potential limitations, making them unsuitable for the detection of aspirin resistance. We investigated whether miR-19b-1-5p could be utilized as a biomarker for aspirin resistance and future major adverse cardio-cerebrovascular (MACCE) events in patients with ACS. Methods and Results In this cohort study, patients with ACS were enrolled from multiple tertiary hospitals in Christchurch, Hong Kong, Sarawak, and Singapore between 2011 and 2015. MiR-19b-1-5p expression was measured from buffy coat of patients with ACS (n=945) by reverse transcription quantitative polymerase chain reaction. Platelet function was determined by Multiplate aggregometry testing. MACCE was collected over a mean follow-up time of 1.01±0.43 years. Low miR-19b-1-5p expression was found to be related to aspirin resistance as could be observed from sustained platelet aggregation in the presence of aspirin (-Log-miR-19b-1-5p, [unstandardized beta, 44.50; 95% CI, 2.20-86.80; P<0.05]), even after adjusting for age, sex, ethnicity, and prior history of stroke. Lower miR-19b-1-5p expression was independently associated with a higher risk of MACCE (-Log-miR-19b-1-5p, [hazard ratio, 1.85; 95% CI, 1.23-2.80; P<0.05]). Furthermore, a significant interaction was noted between the inverse miR-19b-1-5p expression and family history of premature coronary artery disease (P=0.01) on the risk of MACCE. Conclusions Lower miR-19b-1-5p expression was found to be associated with sustained platelet aggregation on aspirin, and a higher risk of MACCE in patients with ACS. Therefore, miR-19b-1-5p could be a suitable marker for aspirin resistance and might predict recurrence of MACCE in patients with ACS.

Matched MeSH terms: Secondary Prevention/methods
Fulltext Comparison of protein expression profiles of different stages of lymph nodes metastasis in breast cancer

Lee HH, Lim CA, Cheong YT, Singh M, Gam LH

Int J Biol Sci, 2012;8(3):353-62.
PMID: 22393307 DOI: 10.7150/ijbs.3157

Breast cancer is the most common cancer among women worldwide. Breast cancer metastasis primarily happens through lymphatic system, where the extent of lymph node metastasis is the major factor influencing staging, prognosis and therapeutic decision of the disease. We aimed to study the protein expression changes in different N (regional lymph nodes) stages of breast cancer. Protein expression profiles of breast cancerous and adjacent normal tissues were mapped by proteomics approach that comprises of two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and tandem mass spectrometry (LC-MS/MS) analysis. Calreticulin and tropomyosin alpha 3 chains were the common up-regulated proteins in N0, N1 and N2 stages of breast cancer. Potential biomarker for each N stage was HSP 70 for N0, 80 k protein H precursor and PDI for N1 stage while 78 kDa glucose-regulated protein was found useful for N2 stage. In addition, significant up-regulation of PDI A3 was detected only in the metastasized breast cancer. The up-regulation expression of these proteins in cancerous tissues can potentially use as indicators for diagnosis, treatment and prognosis of different N stages of breast cancer.

Matched MeSH terms: Carcinoma, Ductal, Breast/secondary*
Fulltext Effect of Cadmium and Copper Exposure on Growth, Secondary Metabolites and Antioxidant Activity in the Medicinal Plant Sambung Nyawa (Gynura procumbens (Lour.) Merr)

Ibrahim MH, Chee Kong Y, Mohd Zain NA

Molecules, 2017 Oct 12;22(10).
PMID: 29023367 DOI: 10.3390/molecules22101623

A randomized complete block (RCBD) study was designed to investigate the effects of cadmium (Cd) and copper (Cu) on the growth, bioaccumulation of the two heavy metals, metabolite content and antibacterial activities in Gyanura procumbens (Lour.) Merr. Nine treatments including (1) control (no Cd and Cu); (2) Cd 2 = cadmium 2 mg/L; (3) Cd 4 = cadmium 4 mg/L; (4) Cu 70 = copper 70 mg/L; (5) Cu 140 = copper 140 mg/L); (6) Cd 2 + Cu 70 = cadmium 2 mg/L + copper 70 mg/L); (7) Cd 2 + Cu 140 = cadmium 2 mg/L + copper 70 mg/L); (8) Cd 4 + Cu 70 = cadmium 4 mg/L+ copper 70 mg/L and (9) Cd 4 + Cu 140 = cadmium 4 mg/L + copper 140 mg/L) were evaluated in this experiment. It was found that the growth parameters (plant dry weight, total leaf area and basal diameter) were reduced with the exposure to increased concentrations of Cd and Cu and further decreased under interaction between Cd and Cu. Production of total phenolics, flavonoids and saponin was observed to be reduced under combined Cd and Cu treatment. The reduction in the production of plant secondary metabolites might be due to lower phenyl alanine lyase (PAL) activity under these conditions. Due to that, the 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferric reducing antioxidant potential (FRAP) and antibacterial activities was also found to be reduced by the combined treatments. The current experiments show that the medicinal properties of G. procumbens are reduced by cadmium and copper contamination. The accumulation of heavy metal also was found to be higher than the safety level recommended by the WHO in the single and combined treatments of Cd and Cu. These results indicate that exposure of G. procumbens to Cd and Cu contaminated soil may potentially harm consumers due to bioaccumulation of metals and reduced efficacy of the herbal product.

Matched MeSH terms: Secondary Metabolism/drug effects*
Structural prediction of a novel laminarinase from the psychrophilic Glaciozyma antarctica PI12 and its temperature adaptation analysis

Parvizpour S, Razmara J, Jomah AF, Shamsir MS, Illias RM

J Mol Model, 2015 Mar;21(3):63.
PMID: 25721655 DOI: 10.1007/s00894-015-2617-1

Here, we present a novel psychrophilic β-glucanase from Glaciozyma antarctica PI12 yeast that has been structurally modeled and analyzed in detail. To our knowledge, this is the first attempt to model a psychrophilic laminarinase from yeast. Because of the low sequence identity (<40%), a threading method was applied to predict a 3D structure of the enzyme using the MODELLER9v12 program. The results of a comparative study using other mesophilic, thermophilic, and hyperthermophilic laminarinases indicated several amino acid substitutions on the surface of psychrophilic laminarinase that totally increased the flexibility of its structure for efficient catalytic reactions at low temperatures. Whereas several structural factors in the overall structure can explain the weak thermal stability, this research suggests that the psychrophilic adaptation and catalytic activity at low temperatures were achieved through existence of longer loops and shorter or broken helices and strands, an increase in the number of aromatic and hydrophobic residues, a reduction in the number of hydrogen bonds and salt bridges, a higher total solvent accessible surface area, and an increase in the exposure of the hydrophobic side chains to the solvent. The results of comparative molecular dynamics simulation and principal component analysis confirmed the above strategies adopted by psychrophilic laminarinase to increase its catalytic efficiency and structural flexibility to be active at cold temperature.

Matched MeSH terms: Protein Structure, Secondary
Fulltext Flavonoids with M1 muscarinic acetylcholine receptor binding activity

Swaminathan M, Chee CF, Chin SP, Buckle MJ, Rahman NA, Doughty SW, et al.

Molecules, 2014 Jun 27;19(7):8933-48.
PMID: 24979399 DOI: 10.3390/molecules19078933

Muscarinic acetylcholine receptor-active compounds have potential for the treatment of Alzheimer's disease. In this study, a series of natural and synthetic flavones and flavonols was assayed in vitro for their ability to inhibit radioligand binding at human cloned M1 muscarinic receptors. Several compounds were found to possess competitive binding affinity (Ki=40-110 µM), comparable to that of acetylcholine (Ki=59 µM). Despite the fact that these compounds lack a positively-charged ammonium group under physiological conditions, molecular modelling studies suggested that they bind to the orthosteric site of the receptor, mainly through non-polar interactions.

Matched MeSH terms: Protein Structure, Secondary
Fulltext Crystal structure and immunological properties of the first annexin from Schistosoma mansoni: insights into the structural integrity of the schistosomal tegument

Leow CY, Willis C, Osman A, Mason L, Simon A, Smith BJ, et al.

FEBS J, 2014 Feb;281(4):1209-25.
PMID: 24428567 DOI: 10.1111/febs.12700

Schistosomiasis is a major parasitic disease of humans, second only to malaria in its global impact. The disease is caused by digenean trematodes that infest the vasculature of their human hosts. These flukes are limited externally by a body wall composed of a syncytial epithelium, the apical surface membrane of which is a parasitism-adapted dual membrane complex. Annexins are thought to be of integral importance for the stability of this apical membrane system. Here, we present the first structural and immunobiochemical characterization of an annexin from Schistosoma mansoni. The crystal structure of annexin B22 confirms the presence of the previously predicted α-helical segment in the II/III linker and reveals a covalently linked head-to-head dimer. From the calcium-bound crystal structure of this protein, canonical type II, type III and B site positions are occupied, and a novel binding site has been identified. The dimer arrangement observed in the crystal structure suggests the presence of two prominent features, a potential non-canonical membrane binding site and a potential binding groove opposite to the former. Results from transcriptional profiling during development show that annexin B22 expression is correlated with life stages of the parasite that possess the syncytial tegument layer, and ultrastructural localization by immuno-electron microscopy confirms the occurrence of annexins in the tegument of S. mansoni. Data from membrane binding and aggregation assays indicate the presence of differential molecular mechanisms and support the hypothesis of annexin B22 providing structural integrity in the tegument.

Matched MeSH terms: Protein Structure, Secondary
Fulltext What is next after transfer of care from hospital to home for stroke patients? Evaluation of a community stroke care service based in a primary care clinic

Aziz AF, Aziz NA, Nordin NA, Ali MF, Sulong S, Aljunid SM

J Neurosci Rural Pract, 2013 Oct;4(4):413-20.
PMID: 24347948 DOI: 10.4103/0976-3147.120243

CONTEXT: Poststroke care in developing countries is inundated with poor concordance and scarce specialist stroke care providers. A primary care-driven health service is an option to ensure optimal care to poststroke patients residing at home in the community.
AIMS: We assessed outcomes of a pilot long-term stroke care clinic which combined secondary prevention and rehabilitation at community level.
SETTINGS AND DESIGN: A prospective observational study of stroke patients treated between 2008 and 2010 at a primary care teaching facility.
SUBJECTS AND METHODS: Analysis of patients was done at initial contact and at 1-year post treatment. Clinical outcomes included stroke risk factor(s) control, depression according to Patient Health Questionnaire (PHQ9), and level of independence using Barthel Index (BI).
STATISTICAL ANALYSIS USED: Differences in means between baseline and post treatment were compared using paired t-tests or Wilcoxon-signed rank test. Significance level was set at 0.05.
RESULTS: Ninety-one patients were analyzed. Their mean age was 62.9 [standard deviation (SD) 10.9] years, mean stroke episodes were 1.30 (SD 0.5). The median interval between acute stroke and first contact with the clinic 4.0 (interquartile range 9.0) months. Mean systolic blood pressure decreased by 9.7 mmHg (t = 2.79, P = 0.007), while mean diastolic blood pressure remained unchanged at 80mmHg (z = 1.87, P = 0.06). Neurorehabilitation treatment was given to 84.6% of the patients. Median BI increased from 81 (range: 2-100) to 90.5 (range: 27-100) (Z = 2.34, P = 0.01). Median PHQ9 scores decreased from 4.0 (range: 0-22) to 3.0 (range: 0-19) though the change was not significant (Z= -0.744, P = 0.457).
CONCLUSIONS: Primary care-driven long-term stroke care services yield favorable outcomes for blood pressure control and functional level.

Matched MeSH terms: Secondary Prevention
Exploring the structural insights on human laforin mutation K87A in Lafora disease--a molecular dynamics study

Srikumar PS, Rohini K

Appl Biochem Biotechnol, 2013 Oct;171(4):874-82.
PMID: 23904258 DOI: 10.1007/s12010-013-0393-x

Lafora disease (LD) is an autosomal recessive, progressive form of myoclonus epilepsy which affects worldwide. LD occurs mainly in countries like southern Europe, northern Africa, South India, and in the Middle East. LD occurs with its onset mainly in teenagers and leads to decline and death within 2 to 10 years. The genes EPM2A and EPM2B are commonly involved in 90 % of LD cases. EPM2A codes for protein laforin which contains an amino terminal carbohydrate binding module (CBM) belonging to the CBM20 family and a carboxy terminal dual specificity phosphatase domain. Mutations in laforin are found to abolish glycogen binding and have been reported in wet lab methods. In order to investigate on structural insights on laforin mutation K81A, we performed molecular dynamics (MD) simulation studies for native and mutant protein. MD simulation results showed loss of stability due to mutation K87A which confirmed the structural reason for conformational changes observed in laforin. The conformational change of mutant laforin was confirmed by analysis using root mean square deviation, root mean square fluctuation, solvent accessibility surface area, radius of gyration, hydrogen bond, and principle component analysis. Our results identified that the flexibility of K87A mutated laforin structure, with replacement of acidic amino acid to aliphatic amino acid in functional CBM domain, have more impact in abolishing glycogen binding that favors LD.

Matched MeSH terms: Protein Structure, Secondary
Molecular dynamics simulations of the adenosine A2a receptor: structural stability, sampling, and convergence

Ng HW, Laughton CA, Doughty SW

J Chem Inf Model, 2013 May 24;53(5):1168-78.
PMID: 23514445 DOI: 10.1021/ci300610w

Molecular dynamics (MD) simulations of membrane-embedded G-protein coupled receptors (GPCRs) have rapidly gained popularity among the molecular simulation community in recent years, a trend which has an obvious link to the tremendous pharmaceutical importance of this group of receptors and the increasing availability of crystal structures. In view of the widespread use of this technique, it is of fundamental importance to ensure the reliability and robustness of the methodologies so they yield valid results and enable sufficiently accurate predictions to be made. In this work, 200 ns simulations of the A2a adenosine receptor (A2a AR) have been produced and evaluated in the light of these requirements. The conformational dynamics of the target protein, as obtained from replicate simulations in both the presence and absence of an inverse agonist ligand (ZM241385), have been investigated and compared using principal component analysis (PCA). Results show that, on this time scale, convergence of the replicates is not readily evident and dependent on the types of the protein motions considered. Thus rates of inter- as opposed to intrahelical relaxation and sampling can be different. When studied individually, we find that helices III and IV have noticeably greater stability than helices I, II, V, VI, and VII in the apo form. The addition of the inverse agonist ligand greatly improves the stability of all helices.

Matched MeSH terms: Protein Structure, Secondary
Fold prediction problem: the application of new physical and physicochemical-based features

Dehzangi A, Phon-Amnuaisuk S

Protein Pept Lett, 2011 Feb;18(2):174-85.
PMID: 21054271

One of the most important goals in bioinformatics is the ability to predict tertiary structure of a protein from its amino acid sequence. In this paper, new feature groups based on the physical and physicochemical properties of amino acids (size of the amino acids' side chains, predicted secondary structure based on normalized frequency of β-Strands, Turns, and Reverse Turns) are proposed to tackle this task. The proposed features are extracted using a modified feature extraction method adapted from Dubchak et al. To study the effectiveness of the proposed features and the modified feature extraction method, AdaBoost.M1, Multi Layer Perceptron (MLP), and Support Vector Machine (SVM) that have been commonly and successfully applied to the protein folding problem are employed. Our experimental results show that the new feature groups altogether with the modified feature extraction method are capable of enhancing the protein fold prediction accuracy better than the previous works found in the literature.

Matched MeSH terms: Protein Structure, Secondary
Deciphering the flexibility and dynamics of Geobacillus zalihae strain T1 lipase at high temperatures by molecular dynamics simulation

Abdul Rahman MB, Karjiban RA, Salleh AB, Jacobs D, Basri M, Thean Chor AL, et al.

Protein Pept Lett, 2009;16(11):1360-70.
PMID: 20001926

The stability of biocatalysts is an important criterion for a sustainable industrial operation economically. T1 lipase is a thermoalkalophilic enzyme derived from Geobacillus zalihae strain T1 (T1 lipase) that was isolated from palm oil mill effluent (POME) in Malaysia. We report here the results of high temperatures molecular dynamics (MD) simulations of T1 lipase in explicit solvent. We found that the N-terminal moiety of this enzyme was accompanied by a large flexibility and dynamics during temperature-induced unfolding simulations which preceded and followed by clear structural changes in two specific regions; the small domain (consisting of helices alpha3 and alpha5, strands beta1 and beta2, and connecting loops) and the main catalytic domain or core domain (consisting of helices alpha6- alpha9 and connecting loops which located above the active site) of the enzyme. The results suggest that the small domain of model enzyme is a critical region to the thermostability of this organism.

Matched MeSH terms: Protein Structure, Secondary
Fulltext Endoscopic cauterization of the sphenopalatine artery in persistent epistaxis

Harvinder S, Rosalind S, Gurdeep S

Med J Malaysia, 2008 Dec;63(5):377-8.
PMID: 19803294 MyJurnal

The management of epistaxis remains to be a challenging problem for most ENT surgeon especially posterior epistaxis. Most cases are managed by placement of posterior nasal packs or balloons and failure leads to more invasive techniques, involving ligation of the internal maxillary artery. The above management is associated with significant patient complication and morbidity. Endoscopic ligation or cauterization of the sphenopalatine artery has emerged as a viable and minimally invasive alternative. We have performed endoscopic cauterization of nine sphenopalatine arteries in eight patients with no further episodes of epistaxis and complications, with an average follow-up of 25 months. The mean age of the patients was 52.75 years. Fifty percent of the patients had a history of hypertension.

Matched MeSH terms: Secondary Prevention
Clinical use of clopidogrel in acute coronary syndrome

Zambahari R, Kwok OH, Javier S, Mak KH, Piyamitr S, Tri Ho HQ, et al.

Int J Clin Pract, 2007 Mar;61(3):473-81.
PMID: 17313616

Several therapeutic approaches have been developed to improve the outcome among patients with acute coronary syndrome (ACS). However, treatment with antithrombotic therapies such as oral glycoprotein IIb/IIIa inhibitors has been limited by the lack of efficacy and excess bleeding complications. As the publication of the landmark study Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE), the clinical benefit of early and intermediate-term use of combined antiplatelet agents--clopidogrel plus aspirin--in non-ST-segment elevation myocardial infarction (NSTEMI) patients became evident. Pretreatment and intermediate-term therapy with clopidogrel in NSTEMI ACS patients undergoing percutaneous coronary intervention (PCI) was further supported by the PCI-CURE trial. Recently, the results of two major trials Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis in Myocardial Infarction 28, Clopidogrel and Metoprolol in Myocardial Infarction Trial established the pivotal role of clopidogrel in the other spectrum of ACS-STEMI. Coupled with the results from previous multicentre trials, these two studies provide a guide for the early and long-term use of clopidogrel in the whole spectrum of ACS. A review summarising the results of the recent clinical trials and a discussion on its implications for the clinical management of ACS is presented.

Matched MeSH terms: Secondary Prevention
Structural analysis of peptides that interact with Newcastle disease virus

Chia SL, Tan WS, Shaari K, Abdul Rahman N, Yusoff K, Satyanarayanajois SD

Peptides, 2006 Jun;27(6):1217-25.
PMID: 16377031

A peptide with the sequence CTLTTKLYC has previously been identified to inhibit the propagation of Newcastle disease virus (NDV) in embryonated chicken eggs and tissue culture. NDV has been classified into two main groups: the velogenic group, and mesogenic with lentogenic strains as the other group based on its dissociation constants. In this study the peptide, CTLTTKLYC, displayed on the pIII protein of a filamentous M13 phage was synthesized and mutated in order to identify the amino acid residues involved in the interactions with NDV. Mutations of C1 and K6 to A1 and A6 did not affect the binding significantly, but substitution of Y8 with A8 dramatically reduced the interaction. This suggests that Y8 plays an important role in the peptide-virus interaction. The three-dimensional structure of the peptide was determined using circular dichroism (CD), nuclear magnetic resonance (NMR), and molecular modeling. The peptide exhibited two possible conformers. One that consists of consecutive beta-turns around T2-L3-T4-T5 and K6-L7-Y8-C9. The other conformer exhibited a beta-hairpin bend type of structure with a bend around L3-T4-T5-K6.

Matched MeSH terms: Protein Structure, Secondary
Crystal structures of Nipah and Hendra virus fusion core proteins

Lou Z, Xu Y, Xiang K, Su N, Qin L, Li X, et al.

FEBS J, 2006 Oct;273(19):4538-47.
PMID: 16972940

The Nipah and Hendra viruses are highly pathogenic paramyxoviruses that recently emerged from flying foxes to cause serious disease outbreaks in humans and livestock in Australia, Malaysia, Singapore and Bangladesh. Their unique genetic constitution, high virulence and wide host range set them apart from other paramyxoviruses. These characteristics have led to their classification into the new genus Henpavirus within the family Paramyxoviridae and to their designation as Biosafety Level 4 pathogens. The fusion protein, an enveloped glycoprotein essential for viral entry, belongs to the family of class I fusion proteins and is characterized by the presence of two heptad repeat (HR) regions, HR1 and HR2. These two regions associate to form a fusion-active hairpin conformation that juxtaposes the viral and cellular membranes to facilitate membrane fusion and enable subsequent viral entry. The Hendra and Nipah virus fusion core proteins were crystallized and their structures determined to 2.2 A resolution. The Nipah and Hendra fusion core structures are six-helix bundles with three HR2 helices packed against the hydrophobic grooves on the surface of a central coiled coil formed by three parallel HR1 helices in an oblique antiparallel manner. Because of the high level of conservation in core regions, it is proposed that the Nipah and Hendra virus fusion cores can provide a model for membrane fusion in all paramyxoviruses. The relatively deep grooves on the surface of the central coiled coil represent a good target site for drug discovery strategies aimed at inhibiting viral entry by blocking hairpin formation.

Matched MeSH terms: Protein Structure, Secondary
Liver transplantation in the Asia Pacific region--trials and tribulations

Fan ST

Med J Malaysia, 2005 Jul;60 Suppl B:1-4.
PMID: 16108164
Matched MeSH terms: Secondary Prevention
Liver transplantation in chronic hepatitis B

Gane E

Med J Malaysia, 2005 Jul;60 Suppl B:88-9.
PMID: 16108183
Matched MeSH terms: Secondary Prevention
A bio-mimetic zinc/tau protein as an artificial catalase

Asadollahi K, Jasemi NS, Riazi GH, Katuli FH, Yazdani F, Sartipnia N, et al.

Int J Biol Macromol, 2016 Nov;92:1307-1312.
PMID: 26905468 DOI: 10.1016/j.ijbiomac.2016.02.045

In this study, the catalase-like activity of monomeric tau protein was reported in the presence of of zinc (Zn(II)) ions at low pH value. Monomeric tau protein contains two SH groups that are a target of disulfide bond formation. However these SH groups are able to interact with Zn(II) ion at pH 7.2 which creates a thiol bond as a mimetic model of chloroperoxidase active site which performs catalase like activity at low pH. Zn(II)/tau protein complex decomposed H2O2 with a high rate (Vm) as well as an efficient turn oven number (kcat) at pH 3. This remarkable catalase like activity is may be attributed to the conformational reorientation of protein at low pH. Circular dichroism (CD) studies did not demonstrate any secondary structural changes of tau protein after addition of Zn(II) ions at pH 7.2. In addition, tau protein shows identical CD bands at pH 7.2 and 3. Moreover, fluorescence quenching of tau by Zn(II) at pH 7.2 was initiated by complex formation rather than by dynamic collision. A significant red shift (6nm) was observed in the emission maximum of the fluorescence spectra when the protein was dissolved at pH 3 compared to pH 7.2. This conformational change can provide information regarding the rearrangements of the protein structure and exposure of Cys-Zn(II) group to the solvent which induces easy access of active site to H2O2 molecules and corresponding enhanced catalytic activity of Zn(II)/tau protein complex. This study introduces tau protein as a bio-inspired high performing scaffold for transition metal encapsulation and introducing an engineered apoprotein-induced biomimetic enzyme.

Matched MeSH terms: Protein Structure, Secondary

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