PDBsum entry 2prb

Transferase

PDB id

2prb

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Contents

			Protein chain

					173 a.a. *

			Ligands

					COA

			Waters ×172

* Residue conservation analysis

PDB id:

2prb

Links

Name:

Transferase

Title:

Crystal structure of aminoglycoside acetyltransferase aac(6')-ib in complex whith coenzyme a

Structure:

Aminoglycoside 6-n-acetyltransferase type ib11. Chain: a. Engineered: yes. Mutation: yes

Source:

Salmonella typhimurium. Organism_taxid: 602. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.80Å

R-factor:

0.210

R-free:

0.226

Authors:

F.Maurice,I.Broutin,I.Podglajen,P.Benas,E.Collatz,F.Dardel

Key ref:

F.Maurice et al. (2008). Enzyme structural plasticity and the emergence of broad-spectrum antibiotic resistance. Embo Rep, 9, 344-349. PubMed id: 18292754 DOI: 10.1038/embor.2008.9

Date:

04-May-07

Release date:

08-Apr-08

PROCHECK

	Headers

	References

Protein chain

Q8GLI5 (Q8GLI5_SALTM) - Aminoglycoside 6-N-acetyltransferase type Ib11 from Salmonella typhimurium

Seq: Struc:					189 a.a. 173 a.a.*

Key:

PfamA domain

Secondary structure

CATH domain

* PDB and UniProt seqs differ at 2 residue positions (black crosses)



		Enzyme reactions

Enzyme class:

E.C.2.3.1.82 - aminoglycoside 6'-N-acetyltransferase.

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

Reaction:

kanamycin B + acetyl-CoA = N(6')-acetylkanamycin B + CoA + H⁺

kanamycin B

acetyl-CoA

N(6')-acetylkanamycin B
Bound ligand (Het Group name = COA)
corresponds exactly

CoA

H(+)

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

reference

DOI no: 10.1038/embor.2008.9	Embo Rep 9:344-349 (2008)
PubMed id: 18292754

Enzyme structural plasticity and the emergence of broad-spectrum antibiotic resistance.
F.Maurice, I.Broutin, I.Podglajen, P.Benas, E.Collatz, F.Dardel.

ABSTRACT

The emergence of multi-resistant pathogenic bacteria is a worldwide health issue. Recently, clinical variants of a single antibiotic-modifying acetyltransferase, AAC(6')-Ib-a variant of aminoglycoside 6'-N-acetyltransferase-have been identified that confer extended resistance to most aminoglycosides and, more surprisingly, to structurally unrelated fluoroquinolones. The corresponding gene is carried by mobile genetic elements and is present in most multi-resistant pathogenic strains, hence making it a serious threat to current therapies. Here, we report the crystal structures of both narrow- and broad-spectrum resistance variants of this enzyme, which reveal the structural basis for the emergence of extended resistance. The active site shows an important plasticity and has adapted to new substrates by a large-scale gaping process. We have also obtained co-crystals with both substrates, and with a simple transition state analogue, which provides new clues for the design of inhibitors of this resistance mechanism.

Literature references that cite this PDB file's key reference

PubMed id

Reference

20564281

G.De Pascale, and G.D.Wright (2010).
Antibiotic resistance by enzyme inactivation: from mechanisms to solutions.

Chembiochem, 11, 1325-1334.

20822442

M.Morar, and G.D.Wright (2010).
The genomic enzymology of antibiotic resistance.

Annu Rev Genet, 44, 25-51.

20833577

M.S.Ramirez, and M.E.Tolmasky (2010).
Aminoglycoside modifying enzymes.

Drug Resist Updat, 13, 151-171.

19164145

G.A.Jacoby, N.Gacharna, T.A.Black, G.H.Miller, and D.C.Hooper (2009).
Temporal appearance of plasmid-mediated quinolone resistance genes.

Antimicrob Agents Chemother, 53, 1665-1666.

19822894

J.Strahilevitz, G.A.Jacoby, D.C.Hooper, and A.Robicsek (2009).
Plasmid-mediated quinolone resistance: a multifaceted threat.

Clin Microbiol Rev, 22, 664-689.

19008944

G.Cambray, and D.Mazel (2008).
Synonymous genes explore different evolutionary landscapes.

PLoS Genet, 4, e1000256.

18710261

M.W.Vetting, C.H.Park, S.S.Hegde, G.A.Jacoby, D.C.Hooper, and J.S.Blanchard (2008).
Mechanistic and structural analysis of aminoglycoside N-acetyltransferase AAC(6')-Ib and its bifunctional, fluoroquinolone-active AAC(6')-Ib-cr variant.

Biochemistry, 47, 9825-9835.

PDB codes:

1v0c 2bue 2vqy

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. Where a reference describes a PDB structure, the PDB codes are shown on the right.