3iof

From Proteopedia

Crystal structure of CphA N220G mutant with inhibitor 10a

PDB ID 3iof

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Structural highlights

3iof is a 1 chain structure with sequence from Aeromonas hydrophila. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.44Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

BLAB_AERHY Can hydrolyze carbapenem compounds.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Although commercialized inhibitors of active site serine beta-lactamases are currently used in coadministration with antibiotic therapy, no clinically useful inhibitors of metallo-beta-lactamases (MBLs) have yet been discovered. In this paper, we investigated the inhibitory effect of mercaptophosphonate derivatives against the three subclasses of MBLs (B1, B2, and B3). All 14 tested mercaptophosphonates, with the exception of 1a, behaved as competitive inhibitors for the three subclasses. Apart from 13 and 21, all the mercaptophosphonates tested exhibit a good inhibitory effect on the subclass B2 MBL CphA with low inhibition constants (K(i) < 15 muM). Interestingly, compound 18 turned out to be a potent broad spectrum MBL inhibitor. The crystallographic structures of the CphA-10a and CphA-18 complexes indicated that the sulfur atom of 10a and the phosphonato group of 18 interact with the Zn(2+) ion, respectively. Molecular modeling studies of the interactions between compounds 10a and 18 and the VIM-4 (B1), CphA (B2), and FEZ-1 (B3) enzymes brought to light different binding modes depending on the enzyme and the inhibitor, consistent with the crystallographic structures.

Mercaptophosphonate Compounds as Broad-Spectrum Inhibitors of the Metallo-beta-lactamases.,Lassaux P, Hamel M, Gulea M, Delbruck H, Mercuri PS, Horsfall L, Dehareng D, Kupper M, Frere JM, Hoffmann K, Galleni M, Bebrone C J Med Chem. 2010 Jun 8. PMID:20527888^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Lassaux P, Hamel M, Gulea M, Delbruck H, Mercuri PS, Horsfall L, Dehareng D, Kupper M, Frere JM, Hoffmann K, Galleni M, Bebrone C. Mercaptophosphonate Compounds as Broad-Spectrum Inhibitors of the Metallo-beta-lactamases. J Med Chem. 2010 Jun 8. PMID:20527888 doi:10.1021/jm100213c