PDBsum entry 3wc5

Hydrolase/hydrolase inhibitor

PDB id: 3wc5

Contents

Protein chain

304 a.a.

Ligands

DDK

CAC

Metals

_ZN ×3

Waters ×340

References listed in PDB file

Key reference

• Title: Structural basis for inhibition of carboxypeptidase b by selenium-Containing inhibitor: selenium coordinates to zinc in enzyme.
• Authors: N.Yoshimoto, T.Itoh, Y.Inaba, H.Ishii, K.Yamamoto.
• Ref.: J Med Chem, 2013, 56, 7527-7535. [DOI no: 10.1021/jm400816v]
• PubMed id: 24010887

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.