PDBsum entry 2i4h

Hydrolase

PDB id: 2i4h

Contents

Protein chain

280 a.a. *

Ligands

UA1

Metals

_MG

_CL

Waters ×182

* Residue conservation analysis

PDB id:

2i4h

Name:

Hydrolase

Title:

Structural studies of protein tyrosine phosphatase beta catalytic domain co-crystallized with a sulfamic acid inhibitor

Structure:

Receptor-type tyrosine-protein phosphatase beta. Chain: a. Fragment: catalytic domain, residues 1662-1973. Synonym: protein-tyrosine phosphatase beta, r-ptp-beta. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ptprb, ptpb. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.15Å R-factor: 0.170 R-free: 0.246

Authors:

A.G.Evdokimov,M.E.Pokross,R.L.Walter,M.Mekel

Key ref:

A.G.Evdokimov et al. (2006). Engineering the catalytic domain of human protein tyrosine phosphatase beta for structure-based drug discovery. Acta Crystallogr D Biol Crystallogr, 62, 1435-1445. PubMed id: 17139078 DOI: 10.1107/S0907444906037784

Date:

21-Aug-06 Release date: 29-Aug-06

Protein chain

P23467  (PTPRB_HUMAN) -  Receptor-type tyrosine-protein phosphatase beta from Homo sapiens

Seq: 1997 a.a.

Struc: 280 a.a.

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

DOI no: 10.1107/S0907444906037784

Acta Crystallogr D Biol Crystallogr 62:1435-1445 (2006)

PubMed id: 17139078

Engineering the catalytic domain of human protein tyrosine phosphatase beta for structure-based drug discovery.

A.G.Evdokimov, M.Pokross, R.Walter, M.Mekel, B.Cox, C.Li, R.Bechard, F.Genbauffe, R.Andrews, C.Diven, B.Howard, V.Rastogi, J.Gray, M.Maier, K.G.Peters.

ABSTRACT

Protein tyrosine phosphatases (PTPs) play roles in many biological processes and are considered to be important targets for drug discovery. As inhibitor development has proven challenging, crystal structure-based design will be very helpful to advance inhibitor potency and selectivity. Successful application of protein crystallography to drug discovery heavily relies on high-quality crystal structures of the protein of interest complexed with pharmaceutically interesting ligands. It is very important to be able to produce protein-ligand crystals rapidly and reproducibly for as many ligands as necessary. This study details our efforts to engineer the catalytic domain of human protein tyrosine phosphatase beta (HPTPbeta-CD) with properties suitable for rapid-turnaround crystallography. Structures of apo HPTPbeta-CD and its complexes with several novel small-molecule inhibitors are presented here for the first time.

Selected figure(s)

Figure 3.
Figure 3 Detailed view of the PTP -CD active site. (a) Hydrogen-bonding network (blue dashes) bridging the ligand (vanadate ion, balls-and-stick representation) and the protein (sticks). (b) Side view depicting additional interactions (magenta dashes) between the ligand and polar residues in the active site. The partial covalent bond between Cys1904 and the V atom is shown as an orange dashed line. (c) Side view of a pTyr mimetic (p-ethyl phenylsulfamic acid) bound in the active site of the enzyme. Relevant hydrogen bonds are shown as colored dashes.

Figure 4.
Figure 4 Transition of the WPD-loop between open (light brown) and closed (green) states. The ligand (sulfamic acid, yellow) is shown in ball-and-stick representation and relevant protein residues are shown as sticks colored according to the loop state. The catalytically important water molecule is shown as a red sphere.

The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2006, 62, 1435-1445) copyright 2006.

Figures were selected by an automated process.