3ram | pdb_00003ram
Crystal structure of HmrA
Structural highlights
Publication Abstract from PubMedHmrA is an antibiotic resistance factor of methicillin-resistant Staphylococcus aureus (MRSA). Molecular analysis of this protein revealed it is not a muramidase or beta-lactamase but an unspecific double-zinc endopeptidase consisting of a catalytic domain and an inserted oligomerization domain, which likely undergo a relative interdomain hinge rotation upon substrate binding. The active-site cleft is located at the domain interface. Four HmrA protomers assemble to a large ~170-kDa homotetrameric complex of 125A. All four active sites are fully accessible and ~50-70A apart, far enough apart to act on a large meshwork substrate independently but simultaneosuly. In vivo studies with four S. aureus strains of variable resistance levels revealed that extracellular addition of HmrA protects against loss of viability in the presence of oxacillin and that this protection depends on proteolytic activity. All these results indicate that HmrA is a peptidase that participates in resistance mechanisms in vivo in the presence of beta-lactams. Furthermore, our results have implication for most S. aureus strains of known genomic sequences and several other cocci and bacilli, which harbor close orthologs. This suggests that HmrA may be a new widespread antibiotic resistance factor in bacteria. Structural and functional analyses reveal that Staphylococcus aureus antibiotic resistance factor HMRA is a zinc-dependent endopeptidase.,Botelho TO, Guevara T, Marrero A, Arede P, Fluxa VS, Reymond JL, Oliveira DC, Gomis-Ruth FX J Biol Chem. 2011 May 27. PMID:21622555[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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