PDBsum entry 1hdu

Carboxypeptidase

PDB id: 1hdu

Contents

Protein chains

307 a.a. *

Ligands

ING ×4

Metals

_ZN ×4

Waters ×591

* Residue conservation analysis

PDB id:

1hdu

Name:

Carboxypeptidase

Title:

Crystal structure of bovine pancreatic carboxypeptidase a complexed with aminocarbonylphenylalanine at 1.75 a

Structure:

Carboxypeptidase a. Chain: a, b, d, e. Ec: 3.4.17.1

Source:

Bos bovis. Bovine. Organism_taxid: 9913. Organ: pancreas

Resolution:

1.75Å R-factor: 0.198 R-free: 0.229

Authors:

J.H.Cho,N.-C.Ha,S.J.Chung,D.H.Kim,K.Y.Choi,B.-H.Oh

Key ref:

J.H.Cho et al. (2002). Insight into the stereochemistry in the inhibition of carboxypeptidase A with N-(hydroxyaminocarbonyl)phenylalanine: binding modes of an enantiomeric pair of the inhibitor to carboxypeptidase A. Bioorg Med Chem Lett, 10, 2015-2022. PubMed id: 11937361 DOI: 10.1016/S0968-0896(01)00429-1

Date:

17-Nov-00 Release date: 15-Nov-01

Protein chains

P00730  (CBPA1_BOVIN) -  Carboxypeptidase A1 from Bos taurus

Seq: 419 a.a.

Struc: 307 a.a.*

* PDB and UniProt seqs differ at 9 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

DOI no: 10.1016/S0968-0896(01)00429-1

Bioorg Med Chem Lett 10:2015-2022 (2002)

PubMed id: 11937361

Insight into the stereochemistry in the inhibition of carboxypeptidase A with N-(hydroxyaminocarbonyl)phenylalanine: binding modes of an enantiomeric pair of the inhibitor to carboxypeptidase A.

J.H.Cho, D.H.Kim, S.J.Chung, N.C.Ha, B.H.Oh, K.Yong Choi.

ABSTRACT

Both D- and L-isomers of N-(hydroxyaminocarbonyl)phenylalanine () were shown to have strong binding affinity towards carboxypeptidase A (CPA) with D- being more potent than its enantiomer by 3-fold (Chung, S. J.; Kim, D. H. Bioorg. Med. Chem. 2001, 9, 185.). In order to understand the reversed stereochemical preference shown in the CPA inhibition, we have solved the crystal structures of CPA complexed with each enantiometer of up to 1.75 A resolution. Inhibitor L- whose stereochemistry belongs to the stereochemical series of substrate binds CPA like substrate does with its carbonyl oxygen coordinating to the active site zinc ion. Its hydroxyl is engaged in hydrogen bonding with the carboxylate of Glu-270. On the other hand, in binding of D- to CPA, its terminal hydroxyl group is involved in interactions with the active site zinc ion and the carboxylate of Glu-270. In both CPA small middle dot complexes, the phenyl ring in is fitted in the substrate recognition pocket at the S(1)' subsite, and the carboxylate of the inhibitors forms bifurcated hydrogen bonds with the guanidinium moiety of Arg-145 and a hydrogen bond with the guanidinium of Arg-127. In the complex of CPA small middle dotD-, the carboxylate of the inhibitor is engaged in hydrogen bonding with the phenolic hydroxyl of the down-positioned Tyr-248. While the L- binding induces a concerted movement of the backbone amino acid residues at the active site, only the downward movement of Tyr-248 was noted when D- binds to CPA.