1fvr

From Proteopedia

---

Revision as of 14:51, 12 November 2007

proteopedia linkproteopedia link

spinqualitylabelsall models 1fvr, resolution 2.2Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

TIE2 KINASE DOMAIN

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

BACKGROUND: Angiogenesis, the formation of new vessels from the existing, vasculature, is a critical process during early development as well as in, a number of disease processes. Tie2 (also known as Tek) is an, endothelium-specific receptor tyrosine kinase involved in both, angiogenesis and vasculature maintenance. RESULTS: We have determined the, crystal structure of the Tie2 kinase domain to 2.2 A resolution. The, structure contains the catalytic core, the kinase insert domain (KID), and, the C-terminal tail. The overall fold is similar to that observed in other, serine/threonine and tyrosine kinase structures; however, several unique, features distinguish the Tie2 structure from those of other kinases. The, Tie2 nucleotide binding loop is in an inhibitory conformation, which is, not seen in other kinase structures, while its activation loop adopts an, "activated-like" conformation in the absence of phosphorylation. Tyr-897, located in the N-terminal domain, may negatively regulate the activity of, Tie2 by preventing dimerization of the kinase domains or by recruiting, phosphatases when it is phosphorylated. CONCLUSION: Regulation of the, kinase activity of Tie2 is a complex process. Conformational changes in, the nucleotide binding loop, activation loop, C helix, and the C-terminal, tail are required for ATP and substrate binding.

Disease

Known diseases associated with this structure: Venous malformations, multiple cutaneous and mucosal OMIM:[600221]

About this Structure

1FVR is a Single protein structure of sequence from Homo sapiens. Active as Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2 Full crystallographic information is available from OCA.

Reference

Structure of the Tie2 RTK domain: self-inhibition by the nucleotide binding loop, activation loop, and C-terminal tail., Shewchuk LM, Hassell AM, Ellis B, Holmes WD, Davis R, Horne EL, Kadwell SH, McKee DD, Moore JT, Structure. 2000 Nov 15;8(11):1105-13. PMID:11080633

Page seeded by OCA on Mon Nov 12 16:57:46 2007