PDBsum entry 1ajq

Antibiotic resistance

PDB id: 1ajq

Contents

Protein chains

206 a.a. *

557 a.a. *

Ligands

SPA

Metals

_CA

Waters ×660

* Residue conservation analysis

PDB id:

1ajq

Name:

Antibiotic resistance

Title:

Penicillin acylase complexed with thiopheneacetic acid

Structure:

Penicillin amidohydrolase. Chain: a. Synonym: penicillin acylase. Penicillin amidohydrolase. Chain: b. Synonym: penicillin acylase. Ec: 3.5.1.11

Source:

Escherichia coli. Organism_taxid: 562. Atcc: 11105. Atcc: 11105

Biol. unit:

Hetero-Dimer (from PDB file)

Resolution:

2.05Å R-factor: 0.165 R-free: 0.233

Authors:

S.H.Done

Key ref:

S.H.Done et al. (1998). Ligand-induced conformational change in penicillin acylase. J Mol Biol, 284, 463-475. PubMed id: 9813130 DOI: 10.1006/jmbi.1998.2180

Date:

07-May-97 Release date: 12-Nov-97

Protein chain

P06875  (PAC_ECOLX) -  Penicillin G acylase from Escherichia coli

Seq: 846 a.a.

Struc: 206 a.a.

Protein chain

P06875  (PAC_ECOLX) -  Penicillin G acylase from Escherichia coli

Seq: 846 a.a.

Struc: 557 a.a.*

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

Enzyme reactions

• Enzyme class: Chains A, B: E.C.3.5.1.11 - penicillin amidase.
• Pathway: Penicillin Biosynthesis and Metabolism
• Reaction: a penicillin + H2O = 6-aminopenicillanate + a carboxylate

penicillin + H2O = 6-aminopenicillanate (Bound ligand (Het Group name = SPA) matches with 53.33% similarity) + carboxylate

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

reference

DOI no: 10.1006/jmbi.1998.2180

J Mol Biol 284:463-475 (1998)

PubMed id: 9813130

Ligand-induced conformational change in penicillin acylase.

S.H.Done, J.A.Brannigan, P.C.Moody, R.E.Hubbard.

ABSTRACT

The enzyme penicillin acylase (penicillin amidohydrolase EC 3.5.1. 11) catalyses the cleavage of the amide bond in the benzylpenicillin (penicillin G) side-chain to produce phenylacetic acid and 6-aminopenicillanic acid (6-APA). The enzyme is of great pharmaceutical importance, as the product 6-APA is the starting point for the synthesis of many semi-synthetic penicillin antibiotics. Studies have shown that the enzyme is specific for hydrolysis of phenylacetamide derivatives, but is more tolerant of features in the rest of the substrate. It is this property that has led to many other applications for the enzyme, and greater knowledge of the enzyme's structure and specificity could facilitate engineering of the enzyme, enhancing its potential for chemical and industrial applications.An extensive study of the binding of a series of phenylacetic acid derivatives has been carried out. A measure of the relative degree of inhibition of the enzyme by each of the compounds has been obtained using a competitive inhibition assay, and the structures of a number of these complexes have been determined by X-ray crystallography. The structures reveal a clear rationale for the observed kinetic results, but show also that some of the ligands cause a conformational change within the binding pocket. This change can generally be understood in terms of the size and orientation of the ligand within the active site.The results reveal that ligand binding in penicillin acylase is facilitated by certain amino acid residues that can adopt two distinct, energetically favourable positions in order to accommodate a variety of compounds within the active site. The structures of these complexes provide evidence for conformational changes in the substrate-binding region that may act as a switch in the mechanism of autocatalytic processing of this enzyme.

Selected figure(s)

Figure 2.
Figure 2. Views showing the electron density and important interactions within the binding site for each of the complexes of the phenylacetic acid derivatives with penicillin acylase. Electron density is a 2F[o] - F[c] map contoured at 1s. Water molecules, where shown, are those that interact with the ligand, and are labelled consistently.

Figure 4.
Figure 4. (a) Stereo representation of p-hydroxyphenylacetic acid from subset 1 (white) and p-nitrophenylacetic from subset 2 (black) structures overlaid and the interactions made by each ligand. Hydrogen bonds for p-nitrophenylacetic acid are shown as dotted lines and H-bonds for the p-hydroxyphenylacetic acid are shown as broken lines. (b) Close up of the overlaid ligand positions from (a).

The above figures are reprinted by permission from Elsevier: J Mol Biol (1998, 284, 463-475) copyright 1998.

Figures were selected by an automated process.