PDBsum entry 2ggc

Hydrolase

PDB id: 2ggc

Contents

Protein chain

263 a.a. *

Ligands

MET

Metals

_CO ×2

_NA

Waters ×345

* Residue conservation analysis

PDB id:

2ggc

Name:

Hydrolase

Title:

Novel bacterial methionine aminopeptidase inhibitors

Structure:

Methionine aminopeptidase. Chain: a. Synonym: map, peptidase m. Engineered: yes

Source:

Escherichia coli k12. Organism_taxid: 83333. Strain: k-12. Gene: map. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

1.00Å R-factor: 0.120 R-free: 0.133

Authors:

A.G.Evdokimov,M.E.Pokross,R.L.Walter,M.Mekel

Key ref:

A.G.Evdokimov et al. (2007). Serendipitous discovery of novel bacterial methionine aminopeptidase inhibitors. Proteins, 66, 538-546. PubMed id: 17120228 DOI: 10.1002/prot.21207

Date:

23-Mar-06 Release date: 13-Jun-06

Protein chain

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

Seq: 264 a.a.

Struc: 263 a.a.

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: 10.1002/prot.21207

Proteins 66:538-546 (2007)

PubMed id: 17120228

Serendipitous discovery of novel bacterial methionine aminopeptidase inhibitors.

A.G.Evdokimov, M.Pokross, R.L.Walter, M.Mekel, B.L.Barnett, J.Amburgey, W.L.Seibel, S.J.Soper, J.F.Djung, N.Fairweather, C.Diven, V.Rastogi, L.Grinius, C.Klanke, R.Siehnel, T.Twinem, R.Andrews, A.Curnow.

ABSTRACT

In this article we describe the application of structural biology methods to the discovery of novel potent inhibitors of methionine aminopeptidases. These enzymes are employed by the cells to cleave the N-terminal methionine from nascent peptides and proteins. As this is one of the critical steps in protein maturation, it is very likely that inhibitors of these enzymes may prove useful as novel antibacterial agents. Involvement of crystallography at the very early stages of the inhibitor design process resulted in serendipitous discovery of a new inhibitor class, the pyrazole-diamines. Atomic-resolution structures of several inhibitors bound to the enzyme illuminate a new mode of inhibitor binding.

Selected figure(s)

Figure 2.
Figure 2. Binding of a PDA (compound 3) to EcMAP. (a) chelation of cobalt atoms (b) mostly hydrophobic interactions between the PDA and the enzyme active site residues. The inhibitor and protein residues are shown as stick models with carbon atoms colored green and yellow, respectively. Cobalt ions are shown as red spheres. Chelation spheres of Co[-]1 and Co[-]2 are shown as yellow and magenta dashes, respectively.

Figure 4.
Figure 4. Interaction of an AA inhibitor with the active site of EcMAP. The inhibitor and protein residues are shown as stick models with carbon atoms colored green and yellow, respectively. Cobalt ions are shown as red spheres. Chelation spheres of Co-1 and Co-2 are shown as yellow and magenta dashes, respectively.

The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (2007, 66, 538-546) copyright 2007.

Figures were selected by an automated process.