PDBsum entry 3wc5

Hydrolase/hydrolase inhibitor

PDB id: 3wc5

Contents

Protein chain

304 a.a.

Ligands

DDK

CAC

Metals

_ZN ×3

Waters ×340

PDB id:

3wc5

Name:

Hydrolase/hydrolase inhibitor

Title:

Carboxypeptidase b in complex with dd9

Structure:

Carboxypeptidase b. Chain: a. Ec: 3.4.17.2

Source:

Sus scrofa. Pig. Organism_taxid: 9823

Resolution:

1.70Å R-factor: 0.191 R-free: 0.224

Authors:

N.Yoshimoto,T.Itoh,Y.Inaba,K.Yamamoto

Key ref:

N.Yoshimoto et al. (2013). Structural basis for inhibition of carboxypeptidase B by selenium-containing inhibitor: selenium coordinates to zinc in enzyme. J Med Chem, 56, 7527-7535. PubMed id: 24010887 DOI: 10.1021/jm400816v

Date:

24-May-13 Release date: 02-Oct-13

Protein chain

P09955  (CBPB1_PIG) -  Carboxypeptidase B from Sus scrofa

Seq: 416 a.a.

Struc: 304 a.a.

Enzyme reactions

• Enzyme class: E.C.3.4.17.2 - carboxypeptidase B.
• Reaction: Peptidyl-L-lysine(or L-arginine) + H(2)O = peptide + L-lysine(or L- arginine)
• Cofactor: Zn(2+)

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

Key reference

DOI no: 10.1021/jm400816v

J Med Chem 56:7527-7535 (2013)

PubMed id: 24010887

Structural basis for inhibition of carboxypeptidase B by selenium-containing inhibitor: selenium coordinates to zinc in enzyme.

N.Yoshimoto, T.Itoh, Y.Inaba, H.Ishii, K.Yamamoto.

ABSTRACT

Activated thrombin-activatable fibrinolysis inhibitor (TAFIa) is a zinc-containing carboxypeptidase and significantly inhibits fibrinolysis. TAFIa inhibitors are thus expected to act as profibrinolytic agents. We recently reported the design and synthesis of selenium-containing inhibitors of TAFIa and their inhibitory activity. Here we report the crystal structures of potent selenium-, sulfur-, and phosphinic acid-containing inhibitors bound to porcine pancreatic carboxypeptidase B (ppCPB). ppCPB is a TAFIa homologue and is surrogate TAFIa for crystallographic analysis. Crystal structures of ppCPB complexed with selenium compound 1a, its sulfur analogue 2, and phosphinic acid derivative EF6265 were determined at 1.70, 2.15, and 1.90 Å resolution, respectively. Each inhibitor binds to the active site of ppCPB in a similar manner to that observed for previously reported inhibitors. Thus, in complexes, selenium, sulfur, and phosphinic acid oxygen coordinate to zinc in ppCPB. This is the first observation and report of selenium coordinating to zinc in CPB.