3QCC

Human receptor protein tyrosine phosphatase gamma, domain 1, in complex with vanadate, orthorhombic crystal form

Summary for 3QCC

• Entry DOI: 10.2210/pdb3qcc/pdb
• Related: 3QCB 3QCD 3QCE 3QCF 3QCG 3QCH 3QCI 3QCJ 3QCK 3QCL 3QCM 3QCN
• Descriptor: Receptor-type tyrosine-protein phosphatase gamma, VANADATE ION (3 entities in total)
• Functional Keywords: tyrosine receptor phosphatase, twisted mixed beta-sheets flanked by {alpha}-helices, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein (Probable): P23470
• Total number of polymer chains: 2
• Total formula weight: 71645.02

Authors

Sheriff, S. (deposition date: 2011-01-16, release date: 2011-12-28, Last modification date: 2023-09-13)

Primary citation

Sheriff, S.,Beno, B.R.,Zhai, W.,Kostich, W.A.,McDonnell, P.A.,Kish, K.,Goldfarb, V.,Gao, M.,Kiefer, S.E.,Yanchunas, J.,Huang, Y.,Shi, S.,Zhu, S.,Dzierba, C.,Bronson, J.,Macor, J.E.,Appiah, K.K.,Westphal, R.S.,O'Connell, J.,Gerritz, S.W.
Small molecule receptor protein tyrosine phosphatase [gamma](RPTP[gamma]) ligands that inhibit phosphatase activity via perturbation of the tryptophan-proline-aspartate (WPD) loop
J.Med.Chem., 54:6548-6562, 2011

PubMed Abstract: Protein tyrosine phosphatases (PTPs) catalyze the dephosphorylation of tyrosine residues, a process that involves a conserved tryptophan-proline-aspartate (WPD) loop in catalysis. In previously determined structures of PTPs, the WPD-loop has been observed in either an "open" conformation or a "closed" conformation. In the current work, X-ray structures of the catalytic domain of receptor-like protein tyrosine phosphatase γ (RPTPγ) revealed a ligand-induced "superopen" conformation not previously reported for PTPs. In the superopen conformation, the ligand acts as an apparent competitive inhibitor and binds in a small hydrophobic pocket adjacent to, but distinct from, the active site. In the open and closed WPD-loop conformations of RPTPγ, the side chain of Trp1026 partially occupies this pocket. In the superopen conformation, Trp1026 is displaced allowing a 3,4-dichlorobenzyl substituent to occupy this site. The bound ligand prevents closure of the WPD-loop over the active site and disrupts the catalytic cycle of the enzyme.

PubMed: 21882820
DOI: 10.1021/jm2003766

Experimental method

X-RAY DIFFRACTION (2.1 Å)