PDBsum entry 2rfh

Hydrolase

PDB id: 2rfh

Contents

Protein chain

307 a.a. *

Ligands

23N

Metals

_ZN

Waters ×198

* Residue conservation analysis

PDB id:

2rfh

Name:

Hydrolase

Title:

Crystal structure analysis of cpa-2-benzyl-3-nitropropanoic acid complex

Structure:

Carboxypeptidase a1. Chain: a. Fragment: ligand binding domain. Ec: 3.4.17.1

Source:

Bos taurus. Bovine. Organ: pancreas

Resolution:

1.70Å R-factor: 0.195 R-free: 0.227

Authors:

S.-F.Wang,Z.-H.Zeng

Key ref:

S.H.Wang et al. (2008). Nitro as a novel zinc-binding group in the inhibition of carboxypeptidase A. Bioorg Med Chem Lett, 16, 3596-3601. PubMed id: 18289863

Date:

29-Sep-07 Release date: 22-Apr-08

Protein chain

P00730  (CBPA1_BOVIN) -  Carboxypeptidase A1 from Bos taurus

Seq: 419 a.a.

Struc: 307 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.4.17.1 - carboxypeptidase A.
• Reaction: Peptidyl-L-amino acid + H₂O = peptide + L-amino acid
• Cofactor: Zn(2+)

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

Added reference

Bioorg Med Chem Lett 16:3596-3601 (2008)

PubMed id: 18289863

Nitro as a novel zinc-binding group in the inhibition of carboxypeptidase A.

S.H.Wang, S.F.Wang, W.Xuan, Z.H.Zeng, J.Y.Jin, J.Ma, G.R.Tian.

ABSTRACT

2-Substituted 3-nitropropanoic acids were designed and synthesized as inhibitors against carboxypeptidase A (CPA). (R)-2-Benzyl- 3-nitropropanoic acid showed a potent inhibition against CPA (K(i)=0.15 microM). X-ray crystallography discloses that the nitro group well mimics the transition state occurred in the hydrolysis catalyzed by CPA, that is, an O,O'-bidentate coordination to the zinc ion and the two respective hydrogen bonds with Glu-270 and Arg-127. Because the nitro group is a planar species, we proposed (R)-2-benzyl-3-nitropropanoic acid as a pseudo-transition-state analog inhibitor against CPA.