PDBsum entry 3blt

Hydrolase

PDB id: 3blt

Contents

Protein chain

282 a.a. *

Ligands

PSY

Waters ×94

* Residue conservation analysis

PDB id:

3blt

Name:

Hydrolase

Title:

Crystal structures of yoph complexed with pvsn and pvs, inhibitors of yoph which co-valent bind to cys of active site

Structure:

Tyrosine-protein phosphatase yoph. Chain: a. Fragment: yoph catalytic domain. Synonym: virulence protein. Engineered: yes

Source:

Yersinia enterocolitica. Organism_taxid: 630. Gene: yoph, yop51. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.20Å R-factor: 0.180 R-free: 0.226

Authors:

S.Liu,Z.-Y.Zhang

Key ref:

S.Liu et al. (2008). Aryl vinyl sulfonates and sulfones as active site-directed and mechanism-based probes for protein tyrosine phosphatases. J Am Chem Soc, 130, 8251-8260. PubMed id: 18528979

Date:

11-Dec-07 Release date: 10-Feb-09

Protein chain

P15273  (YOPH_YEREN) -  Tyrosine-protein phosphatase YopH from Yersinia enterocolitica

Seq: 468 a.a.

Struc: 282 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.3.1.3.48 - protein-tyrosine-phosphatase.
• Reaction: O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Key reference

J Am Chem Soc 130:8251-8260 (2008)

PubMed id: 18528979

Aryl vinyl sulfonates and sulfones as active site-directed and mechanism-based probes for protein tyrosine phosphatases.

S.Liu, B.Zhou, H.Yang, Y.He, Z.X.Jiang, S.Kumar, L.Wu, Z.Y.Zhang.

ABSTRACT

Protein tyrosine phosphatases (PTPs) play key roles in the regulation of normal and pathological processes ranging from cell proliferation, differentiation, metabolism, and survival to many human diseases including cancer and diabetes. Functional studies of PTP can be greatly facilitated by small molecule probes that covalently label the active site of a PTP through an activity-dependent chemical reaction. In this article, we characterize phenyl vinyl sulfonate (PVSN) and phenyl vinyl sulfone (PVS) as a new class of mechanism-based PTP probes. PVSN and PVS inactivate a broad range of PTPs in a time- and concentration-dependent fashion. The PVSN- and PVS-mediated PTP inactivation is active site-directed and irreversible, resulting from a Michael addition of the active-site Cys Sgamma onto the terminal carbon of the vinyl group. Structural and mechanistic analyses reveal the molecular basis for the preference of PVSN/PVS toward the PTPs, which lies in the ability of PVSN and PVS to engage the conserved structural and catalytic machinery of the PTP active site. In contrast to early alpha-bromobenzyl phosphonate-based probes, PVSN and PVS are resistant to solvolysis and are cell-permeable and thus hold promise for in vivo applications. Collectively, these properties bode well for the development of aryl vinyl sulfonate/sulfone-based PTP probes to interrogate PTP activity in complex proteomes.