PDBsum entry 1c22

Hydrolase

PDB id: 1c22

Contents

Protein chain

262 a.a. *

Ligands

MF3

Metals

_CO ×2

_NA

Waters ×103

* Residue conservation analysis

PDB id:

1c22

Name:

Hydrolase

Title:

E. Coli methionine aminopeptidase: trifluoromethionine complex

Structure:

Methionine aminopeptidase. Chain: a. Engineered: yes. Mutation: yes. Other_details: trifluoromethionine complex

Source:

Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.75Å R-factor: 0.163

Authors:

W.T.Lowther,Y.Zhang,P.B.Sampson,J.F.Honek,B.W.Matthews

Key ref:

W.T.Lowther et al. (1999). Insights into the mechanism of Escherichia coli methionine aminopeptidase from the structural analysis of reaction products and phosphorus-based transition-state analogues. Biochemistry, 38, 14810-14819. PubMed id: 10555963 DOI: 10.1021/bi991711g

Date:

22-Jul-99 Release date: 17-Nov-99

Protein chain

P0AE18  (MAP1_ECOLI) -  Methionine aminopeptidase from Escherichia coli (strain K12)

Seq: 264 a.a.

Struc: 262 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.3.4.11.18 - methionyl aminopeptidase.
• Reaction: Release of N-terminal amino acids, preferentially methionine, from peptides and arylamides.
• Cofactor: Cobalt cation

DOI no: 10.1021/bi991711g

Biochemistry 38:14810-14819 (1999)

PubMed id: 10555963

Insights into the mechanism of Escherichia coli methionine aminopeptidase from the structural analysis of reaction products and phosphorus-based transition-state analogues.

W.T.Lowther, Y.Zhang, P.B.Sampson, J.F.Honek, B.W.Matthews.

ABSTRACT

In an effort to differentiate between alternative mechanistic schemes that have been postulated for Escherichia coli methionine aminopeptidase (eMetAP), the modes of binding of a series of products and phosphorus-based transition-state analogues were determined by X-ray crystallography. Methionine phosphonate, norleucine phosphonate, and methionine phosphinate bind with the N-terminal group interacting with Co2 and with the respective phosphorus oxygens binding between the metals, interacting in a bifurcated manner with Co1 and His178 and hydrogen bonded to His79. In contrast, the reaction product methionine and its analogue trifluoromethionine lose interactions with Co1 and His79. The interactions with the transition-state analogues are, in general, very similar to those seen previously for the complex of the enzyme with a bestatin-based inhibitor. The mode of interaction of His79 is, however, different. In the case of the bestatin-based inhibitor, His79 interacts with atoms in the peptide bond between the P(1)' and P(2)' residues. In the present transition-state analogues, however, the histidine moves 1.2 A toward the metal center and hydrogen bonds with the atom that corresponds to the nitrogen of the scissile peptide bond (i.e., between the P(1) and P(1)' residues). These observations tend to support one of the mechanistic schemes for eMetAP considered before, although with a revision in the role played by His79. The results also suggest parallels between the mechanism of action of methionine aminopeptidase and other "pita-bread" enzymes including aminopeptidase P and creatinase.