3RAM: Crystal Structure Of Hmra

HmrA is an antibiotic resistance factor of methicillin-resistant Staphylococcus aureus. Molecular analysis of this protein revealed that it is not a muramidase or beta-lactamase but a nonspecific double-zinc endopeptidase consisting of a catalytic domain and an inserted oligomerization domain, which probably 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 approximately 170-kDa homotetrameric complex of 125 A. All four active sites are fully accessible and approximately 50-70 A apart, far enough apart to act on a large meshwork substrate independently but simultaneously. In vivo studies with four S. aureus strains of variable resistance levels revealed that the extracellular addition of HmrA protects against loss of viability in the presence of oxacillin and that this protection depends on proteolytic activity. All of 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 implications 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.
PDB ID: 3RAMDownload
MMDB ID: 90859
PDB Deposition Date: 2011/3/28
Updated in MMDB: 2011/08
Experimental Method:
x-ray diffraction
Resolution: 2.7  Å
Source Organism:
Similar Structures:
Biological Unit for 3RAM: tetrameric; determined by author and by software (PISA)
Molecular Components in 3RAM
Label Count Molecule
Proteins (4 molecules)
Hmra Protein
Molecule annotation
Chemicals (41 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB