PDBsum entry 2rcx

Hydrolase

PDB id

2rcx

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Contents

			Protein chains

					358 a.a. *

			Ligands

					SM4-PO4


					PO4


					SM4

			Waters ×482

* Residue conservation analysis

PDB id:

2rcx

Links

Name:

Hydrolase

Title:

Ampc beta-lactamase in complex with (1r)-1-(2-thiophen-2-yl- acetylamino)-1-(3-(2-carboxyvinyl)-phenyl) methylboronic acid

Structure:

Beta-lactamase. Chain: a, b. Synonym: cephalosporinase. Engineered: yes

Source:

Escherichia coli. Organism_taxid: 562. Gene: ampc, ampa. Expressed in: escherichia coli k12. Expression_system_taxid: 83333.

Resolution:

2.00Å

R-factor:

0.176

R-free:

0.219

Authors:

F.Morandi,S.Morandi,F.Prati,B.K.Shoichet

Key ref:

S.Morandi et al. (2008). Structure-based optimization of cephalothin-analogue boronic acids as beta-lactamase inhibitors. Bioorg Med Chem Lett, 16, 1195-1205. PubMed id: 17997318 DOI: 10.1016/j.bmc.2007.10.075

Date:

20-Sep-07

Release date:

27-Nov-07

PROCHECK

	Headers

	References

Protein chains

P00811 (AMPC_ECOLI) - Beta-lactamase from Escherichia coli (strain K12)

Seq: Struc:					377 a.a. 358 a.a.

Key:

PfamA domain

Secondary structure

CATH domain



		Enzyme reactions

Enzyme class:

E.C.3.5.2.6 - beta-lactamase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Pathway:

Penicillin Biosynthesis and Metabolism

Reaction:

a beta-lactam + H2O = a substituted beta-amino acid

Cofactor:

Zn(2+)

DOI no: 10.1016/j.bmc.2007.10.075	Bioorg Med Chem Lett 16:1195-1205 (2008)
PubMed id: 17997318

Structure-based optimization of cephalothin-analogue boronic acids as beta-lactamase inhibitors.
S.Morandi, F.Morandi, E.Caselli, B.K.Shoichet, F.Prati.

ABSTRACT

Boronic acids have proved to be promising selective inhibitors of beta-lactamases, acting as transition state analogues. Starting from a previously described nanomolar inhibitor of AmpC beta-lactamase, three new inhibitors were designed to gain interactions with highly conserved residues, such as Asn343, and to bind more tightly to the enzyme. Among these, one was obtained by stereoselective synthesis and succeeded in placing its anionic group into the carboxylate binding site of the enzyme, as revealed by X-ray crystallography of the complex inhibitor/AmpC. Nevertheless, it failed at improving affinity, when compared to the lead from which it was derived. The origins of this structural and energetic discrepancy are discussed.

Literature references that cite this PDB file's key reference

PubMed id

Reference

20394454

C.Bebrone, P.Lassaux, L.Vercheval, J.S.Sohier, A.Jehaes, E.Sauvage, and M.Galleni (2010).
Current challenges in antimicrobial chemotherapy: focus on ß-lactamase inhibition.

Drugs, 70, 651-679.

19925018

S.M.Drawz, M.Babic, C.R.Bethel, M.Taracila, A.M.Distler, C.Ori, E.Caselli, F.Prati, and R.A.Bonomo (2010).
Inhibition of the class C beta-lactamase from Acinetobacter spp.: insights into effective inhibitor design.

Biochemistry, 49, 329-340.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.