Modelling Structures of Proteins and their Complexes

EZH2 promotes neoplastic transformation through VAV interaction-dependent extranuclear mechanisms

Recently, we reported that the histone methyltransferase, EZH2, controls leukocyte migration through interaction with the cytoskeleton remodeling effector, VAV, and direct methylation of the cytoskeletal regulatory protein, Talin. However, it is unclear whether this extranuclear, epigenetic-independent function of EZH2 has a profound impact on the initiation of cellular transformation and metastasis. Here, we show that EZH2 increases Talin1 methylation and cleavage, thereby enhancing adhesion turnover and promoting accelerated tumorigenesis.

type: 
Journal Paper
journal: 
Oncogene 2017, Pg 1-17, doi:10.1038/onc.2017.309
pubmed: 
28967906
Url: 
http://www.nature.com.ejproxy.a-star.edu.sg/articles/onc2017309
Impact Factor: 
7.519
Date of acceptance: 
2017-07-11

Depth: a web server to compute depth, cavity sizes, detect potential small-molecule ligand-binding cavities and predict the pKa of ionizable residues in proteins

Residue depth accurately measures burial and parameterizes local protein environment. Depth is the distance of any atom/residue to the closest bulk water. We consider the non-bulk waters to occupy cavities, whose volumes are determined using a Voronoi procedure. Our estimation of cavity sizes is statistically superior to estimates made by CASTp and VOIDOO, and on par with McVol over a data set of 40 cavities. Our calculated cavity volumes correlated best with the experimentally determined destabilization of 34 mutants from five proteins.

type: 
Journal Paper
journal: 
Nucleic Acids Research 2013, Vol. 41, Pg 314-321, doi:10.1093/nar/gkt503
pubmed: 
23766289
Url: 
http://www.ncbi.nlm.nih.gov/pubmed/23766289
Date of acceptance: 
2013-05-15

X-ray crystal structure of HLA-DQ2 in complex with CLIP1 and CLIP2 (P5026)

The class II MHC protein HLA-DQ2 is strongly associated with type 1 diabetes and celiac disease. CLIP (MHC class II-associated invariant chain peptide) occupies the peptide binding groove of all newly synthesized class II MHC proteins until HLA-DM replaces it with an antigen peptide. We have determined the atomic structure of HLA-DQ2-CLIP1 and HLA-DQ2-CLIP2 complex at 2.8 Ang and 2.2 Ang, respectively. Our crystal structure shows that MRMATPLLM of CLIP1 occupies the P1 to P9 pockets of HLA-DQ2. For CLIP2, PLLMQALPM occupies the P1 to P9 pockets of HLA-DQ2.

type: 
Conference Paper/Poster
journal: 
The Journal of Immunology May 2013, Issue no. 190, 41.14
Url: 
http://jimmunol.org/cgi/content/meeting_abstract/190/1_MeetingAbstracts/41.14

Transplantation of a hydrogen bonding network from West Nile virus protease onto Dengue-2 protease improves catalytic efficiency and sheds light on substrate specificity.

The two-component serine protease of flaviviruses such as Dengue virus (DENV) and West Nile virus (WNV) are attractive targets for inhibitor/therapeutic design. Peptide aldehyde inhibitors that bind to the covalently tethered two-component WNV protease (WNVpro) with 50% inhibitory concentration (IC50) at sub-micromolar concentrations,bind the equivalent DENV-2 protease

type: 
Journal Paper
journal: 
Protein Engineering, Design & Selection, 2012,, Vol. 25, No. 12, Pg 843-850, doi: 10.1093/protein/gzs049. Epub 2012 Sep 12
pubmed: 
22972763
Impact Factor: 
2.937

SALIGN: a web server for alignment of multiple protein sequences and structures

ABSTRACT
Summary: Accurate alignment of protein sequences and/or structures is crucial for many biological analyses, including
functional annotation of proteins, classifying protein sequences into families, and comparative protein structure modeling. Described
here is a web interface to SALIGN, the versatile protein multiple sequence/structure alignment module of MODELLER. The web
server automatically determines the best alignment procedure based on the inputs, while allowing the user to override default parameter

type: 
Journal Paper
journal: 
Bioinformatics. 2012 Aug 1;28(15):2072-3. doi: 10.1093/bioinformatics/bts302
pubmed: 
22618536
Impact Factor: 
5.468

Biological insights from topology independent comparison of protein 3D structures

type: 
Journal Paper
journal: 
Nucleic Acids Res. 2011 Aug;39(14):e94
pubmed: 
21596786
Url: 
http://www.ncbi.nlm.nih.gov/pubmed/21596786
Impact Factor: 
7.836

Functional analysis of pharmacogenetic variants of human organic cation/carnitine transporter 2 (hOCTN2) identified in Singaporean populations

The human organic cation/carnitine transporter-2 (hOCTN2; SLC22A5) mediates the cellular influx of organic cations such as carnitine, which is essential for fatty acid oxidation. Primary carnitine deficiency has been associated with a wide range of hOCTN2 gene mutations. Six novel nonsynonymous single nucleotide polymorphisms in the hOCTN2 gene were identified recently in Chinese and Indian populations of Singapore. The present study evaluated the impact of these polymorphisms on hOCTN2 function and expression in HEK-293 cells.

type: 
Journal Paper
journal: 
Biochemical Pharmacology 2011, doi: 10.1016/j.bcp.2011.08.008
pubmed: 
21864509
Url: 
http://www.ncbi.nlm.nih.gov/pubmed/21864509
Impact Factor: 
4.889
Date of acceptance: 
2011-08-16

DEPTH: a web server to compute depth and predict small-molecule binding cavities in proteins

type: 
Journal Paper
journal: 
Nucleic Acids Res. 2011 Jul;39:W242-8
pubmed: 
21576233
Url: 
http://www.ncbi.nlm.nih.gov/pubmed/21576233
Impact Factor: 
7.836

CLICK--topology-independent comparison of biomolecular 3D structures

type: 
Journal Paper
journal: 
Nucleic Acids Res. 2011 Jul;39:W24-8
pubmed: 
21602266
Url: 
http://www.ncbi.nlm.nih.gov/pubmed/21602266
Impact Factor: 
7.836

Toward better understanding of protein secondary structure: extracting prediction rules

type: 
Journal Paper
journal: 
IEEE/ACM Trans Comput Biol Bioinform. 2011 May-Jun;8(3):858-64
pubmed: 
21393657
Url: 
http://www.ncbi.nlm.nih.gov/pubmed/21393657
Impact Factor: 
1.664
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