PDBsum entry: 1ymk

Hydrolase, cell cycle

PDB id: 1ymk

Contents

Protein chain

171 a.a. *

Metals

_CL

Waters ×190

* Residue conservation analysis

PDB id:

1ymk

Name:

Hydrolase, cell cycle

Title:

Crystal structure of the cdc25b phosphatase catalytic domain in the apo form

Structure:

M-phase inducer phosphatase 2. Chain: a. Fragment: catalytic domain. Synonym: cdc25b phosphatase. Dual specificity phosphatase cdc25b. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: cdc25b, cdc25hu2. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.70Å R-factor: 0.178 R-free: 0.196

Authors:

G.K.Buhrman,B.Parker,J.Sohn,J.Rudolph,C.Mattos

Key ref:

G.Buhrman et al. (2005). Structural mechanism of oxidative regulation of the phosphatase Cdc25B via an intramolecular disulfide bond. Biochemistry, 44, 5307-5316. PubMed id: 15807524 DOI: 10.1021/bi047449f

Date:

21-Jan-05 Release date: 12-Apr-05

Protein chain

P30305  (MPIP2_HUMAN) -  M-phase inducer phosphatase 2

Seq: 580 a.a.

Struc: 171 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: Protein tyrosine phosphate + H₂O = protein tyrosine + phosphate

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

 Gene Ontology (GO) functional annotation 

• Cellular component: intracellular (1 term)
• Biological process: M phase of mitotic cell cycle (2 terms)
• Biochemical function: protein tyrosine phosphatase activity (1 term)

reference

DOI no: 10.1021/bi047449f

Biochemistry 44:5307-5316 (2005)

PubMed id: 15807524

Structural mechanism of oxidative regulation of the phosphatase Cdc25B via an intramolecular disulfide bond.

G.Buhrman, B.Parker, J.Sohn, J.Rudolph, C.Mattos.

ABSTRACT

Cdc25B phosphatase, an important regulator of the cell cycle, forms an intramolecular disulfide bond in response to oxidation leading to reversible inactivation of phosphatase activity. We have obtained a crystallographic time course revealing the structural rearrangements that occur in the P-loop as the enzyme goes from its apo state, through the sulfenic (Cys-SO(-)) intermediate, to the stable disulfide. We have also obtained the structures of the irreversibly oxidized sulfinic (Cys-SO(2)(-)) and sulfonic (Cys-SO(3)(-)) Cdc25B. The active site P-loop is found in three conformations. In the apoenzyme, the P-loop is in the active conformation. In the sulfenic intermediate, the P-loop partially obstructs the active site cysteine, poised to undergo the conformational changes that accompany disulfide bond formation. In the disulfide form, the P-loop is closed over the active site cysteine, resulting in an enzyme that is unable to bind substrate. The structural changes that occur in the sulfenic intermediate of Cdc25B are distinctly different from those seen in protein tyrosine phosphatase 1B where a five-membered sulfenyl amide ring is generated as the stable end product. This work elucidates the mechanism by which chemistry and structure are coupled in the regulation of Cdc25B by reactive oxygen species.