Modelling Structures of Proteins and their Complexes

EZH2 promotes neoplastic transformation through VAV interaction-dependent extranuclear mechanisms

Published date : 02 Oct 2017

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
Impact Factor
7.519

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

Published date : 12 Jun 2013

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

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

Published date : 01 May 2013

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

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

Published date : 12 Sep 2012

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
Impact Factor
2.937

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

Published date : 21 May 2012

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
Impact Factor
5.468

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

Published date : 30 Aug 2011

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
Impact Factor
4.889