PDBsum entry 1cps

HydrolasE(C-terminal peptidase)

PDB id: 1cps

Contents

Protein chain

307 a.a. *

Ligands

CPM

Metals

_ZN

Waters ×122

* Residue conservation analysis

PDB id:

1cps

Name:

HydrolasE(C-terminal peptidase)

Title:

Structural comparison of sulfodiimine and sulfonamide inhibitors in their complexes with zinc enzymes

Structure:

Carboxypeptidase a. Chain: a. Engineered: yes

Source:

Bos taurus. Cattle. Organism_taxid: 9913

Resolution:

2.25Å R-factor: 0.174

Authors:

A.M.Cappalonga,R.S.Alexander,D.W.Christianson

Key ref:

A.M.Cappalonga et al. (1992). Structural comparison of sulfodiimine and sulfonamide inhibitors in their complexes with zinc enzymes. J Biol Chem, 267, 19192-19197. PubMed id: 1527041

Date:

18-Feb-92 Release date: 31-Oct-93

Protein chain

P00730  (CBPA1_BOVIN) -  Carboxypeptidase A1 from Bos taurus

Seq: 419 a.a.

Struc: 307 a.a.*

* PDB and UniProt seqs differ at 7 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

J Biol Chem 267:19192-19197 (1992)

PubMed id: 1527041

Structural comparison of sulfodiimine and sulfonamide inhibitors in their complexes with zinc enzymes.

A.M.Cappalonga, R.S.Alexander, D.W.Christianson.

ABSTRACT

The three-dimensional structure of (L(-)-2-carboxy-3-phenylpropyl) methylsulfodiimine in its complex with the zinc metalloenzyme carboxypeptidase A has been determined at 2.25-A resolution by x-ray crystallographic methods. This is the first example of a sulfodiimine-containing inhibitor binding to a zinc enzyme, and the structure of the enzyme-inhibitor complex reveals that the tetrahedral sulfodiimine group coordinates to the active site zinc ion in unidentate fashion. The zinc-coordinated nitrogen atom of the sulfodiimine group is also within hydrogen bonding distance to active site base Glu-270; presumably, the sulfodiimine is ionized and accepts a hydrogen bond from protonated Glu-270. The other sulfodiimine nitrogen accepts a hydrogen bond from Arg-127, and the inhibitor binds as a possible analogue of the tetrahedral transition state (or intermediate) in a promoted water pathway for peptide hydrolysis. The unidentate sulfodiimine-zinc binding mode observed in this enzyme-inhibitor complex is reminiscent of that observed in sulfonamide complexes with the zinc metalloenzyme carbonic anhydrase II, and the structural features of sulfodiimine- and sulfonamide-zinc interactions exhibit important similarities among recently determined structures of enzyme-inhibitor complexes: ionized nitrogens bind to zinc in each structure, and these nitrogens are engaged in hydrogen bond interactions with neighboring enzyme residues.