2a8b

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:2a8b.gif|left|200px]]
+
{{Seed}}
 +
[[Image:2a8b.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_2a8b| PDB=2a8b | SCENE= }}
{{STRUCTURE_2a8b| PDB=2a8b | SCENE= }}
-
'''Crystal Structure of the Catalytic Domain of Human Tyrosine Phosphatase Receptor, Type R'''
+
===Crystal Structure of the Catalytic Domain of Human Tyrosine Phosphatase Receptor, Type R===
-
==Overview==
+
<!--
-
Protein tyrosine phosphatases PTPN5, PTPRR and PTPN7 comprise a family of phosphatases that specifically inactivate MAPKs (mitogen-activated protein kinases). We have determined high-resolution structures of all of the human family members, screened them against a library of 24000 compounds and identified two classes of inhibitors, cyclopenta[c]quinolinecarboxylic acids and 2,5-dimethylpyrrolyl benzoic acids. Comparative structural analysis revealed significant differences within this conserved family that could be explored for the design of selective inhibitors. PTPN5 crystallized, in two distinct crystal forms, with a sulphate ion in close proximity to the active site and the WPD (Trp-Pro-Asp) loop in a unique conformation, not seen in other PTPs, ending in a 3(10)-helix. In the PTPN7 structure, the WPD loop was in the closed conformation and part of the KIM (kinase-interaction motif) was visible, which forms an N-terminal aliphatic helix with the phosphorylation site Thr66 in an accessible position. The WPD loop of PTPRR was open; however, in contrast with the structure of its mouse homologue, PTPSL, a salt bridge between the conserved lysine and aspartate residues, which has been postulated to confer a more rigid loop structure, thereby modulating activity in PTPSL, does not form in PTPRR. One of the identified inhibitor scaffolds, cyclopenta[c]quinoline, was docked successfully into PTPRR, suggesting several possibilities for hit expansion. The determined structures together with the established SAR (structure-activity relationship) propose new avenues for the development of selective inhibitors that may have therapeutic potential for treating neurodegenerative diseases in the case of PTPRR or acute myeloblastic leukaemia targeting PTPN7.
+
The line below this paragraph, {{ABSTRACT_PUBMED_16441242}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 16441242 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_16441242}}
==About this Structure==
==About this Structure==
Line 40: Line 44:
[[Category: Structural genomic]]
[[Category: Structural genomic]]
[[Category: Structural genomics consortium]]
[[Category: Structural genomics consortium]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu May 22 22:18:40 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 07:34:59 2008''

Revision as of 04:35, 28 July 2008

Image:2a8b.png

Template:STRUCTURE 2a8b

Crystal Structure of the Catalytic Domain of Human Tyrosine Phosphatase Receptor, Type R

Template:ABSTRACT PUBMED 16441242

About this Structure

2A8B is a Single protein structure of sequence from Homo sapiens. This structure supersedes the now removed PDB entry 1zep. Full crystallographic information is available from OCA.

Reference

Crystal structures and inhibitor identification for PTPN5, PTPRR and PTPN7: a family of human MAPK-specific protein tyrosine phosphatases., Eswaran J, von Kries JP, Marsden B, Longman E, Debreczeni JE, Ugochukwu E, Turnbull A, Lee WH, Knapp S, Barr AJ, Biochem J. 2006 May 1;395(3):483-91. PMID:16441242

Page seeded by OCA on Mon Jul 28 07:34:59 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2a8b"
Personal tools