NDLI: Distinct functional and conformational states of the human lymphoid tyrosine phosphatase catalytic domain can be targeted by choice of the inhibitor chemotype

Content Provider	Springer Nature Link
Author	Vidović, Dušica Xie, Yuli Rinderspacher, Alison Deng, Shi Xian Landry, Donald W. Chung, Caty Smith, Deborah H. Tautz, Lutz Schürer, Stephan C.
Copyright Year	2011
Abstract	The lymphoid tyrosine phosphatase (LYP), encoded by the PTPN22 gene, has recently been identified as a promising drug target for human autoimmunity diseases. Like the majority of protein-tyrosine phosphatases LYP can adopt two functionally distinct forms determined by the conformation of the WPD-loop. The WPD-loop plays an important role in the catalytic dephosphorylation by protein-tyrosine phosphatases. Here we investigate the binding modes of two chemotypes of small molecule LYP inhibitors with respect to both protein conformations using computational modeling. To evaluate binding in the active form, we built a LYP protein structure model of high quality. Our results suggest that the two different compound classes investigated, bind to different conformations of the LYP phosphatase domain. Binding to the closed form is facilitated by an interaction with Asp195 in the WPD-loop, presumably stabilizing the active conformation. The analysis presented here is relevant for the design of inhibitors that specifically target either the closed or the open conformation of LYP in order to achieve better selectivity over phosphatases with similar binding sites.
Starting Page	873
Ending Page	883
Page Count	11
File Format	PDF
ISSN	0920654X
Journal	Journal of Computer-Aided Molecular Design
Volume Number	25
Issue Number	9
e-ISSN	15734951
Language	English
Publisher	Springer Netherlands
Publisher Date	2011-09-09
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Protein tyrosine phosphorylation PTPN22 LYP Drug design Docking Homology modeling Animal Anatomy / Morphology / Histology Computer Applications in Chemistry Physical Chemistry
Content Type	Text
Resource Type	Article
Subject	Drug Discovery Physical and Theoretical Chemistry Computer Science Applications

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Identification and structure–function analyses of an allosteric inhibitor of the tyrosine phosphatase PTPN22

Genetic Association Between a Lymphoid Tyrosine Phosphatase (PTPN22) and Type 1 Diabetes

Homology modeling, docking and structure-based pharmacophore of inhibitors of DNA methyltransferase

Ligand-guided optimization of CXCR4 homology models for virtual screening using a multiple chemotype approach

Homology modeling of 5-lipoxygenase and hints for better inhibitor design

Conformational analysis of a farnesyltransferase peptide inhibitor, CVIM

Refined homology model of monoacylglycerol lipase: toward a selective inhibitor

Structure-based design of Aurora A & B inhibitors

Molecular modeling study of the induced-fit effect on kinase inhibition: the case of fibroblast growth factor receptor 3 (FGFR3)

Distinct functional and conformational states of the human lymphoid tyrosine phosphatase catalytic domain can be targeted by choice of the inhibitor chemotype

Similar Documents

Identification and structure–function analyses of an allosteric inhibitor of the tyrosine phosphatase PTPN22

Genetic Association Between a Lymphoid Tyrosine Phosphatase (PTPN22) and Type 1 Diabetes

Homology modeling, docking and structure-based pharmacophore of inhibitors of DNA methyltransferase

Ligand-guided optimization of CXCR4 homology models for virtual screening using a multiple chemotype approach

Homology modeling of 5-lipoxygenase and hints for better inhibitor design

Conformational analysis of a farnesyltransferase peptide inhibitor, CVIM

Refined homology model of monoacylglycerol lipase: toward a selective inhibitor

Structure-based design of Aurora A & B inhibitors

Molecular modeling study of the induced-fit effect on kinase inhibition: the case of fibroblast growth factor receptor 3 (FGFR3)

Distinct functional and conformational states of the human lymphoid tyrosine phosphatase catalytic domain can be targeted by choice of the inhibitor chemotype