3RAM

Crystal structure of HmrA

3RAM の概要

• エントリーDOI: 10.2210/pdb3ram/pdb
• 分子名称: HmrA protein, ZINC ION, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: two-domain, catalytic (alpha-beta-alpha) motif, tetramerisation (alpha, beta, alpha), endoprotease, hydrolase
• 由来する生物種: Staphylococcus aureus
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 176357.93

構造登録者

Botelho, T.,Guevara, T.,Marrero, A.,Gomis-Ruth, F.X. (登録日: 2011-03-28, 公開日: 2011-05-25, 最終更新日: 2024-11-20)

主引用文献

Botelho, T.O.,Guevara, T.,Marrero, A.,Arede, P.,Fluxa, V.S.,Reymond, J.L.,Oliveira, D.C.,Gomis-Ruth, F.X.
Structural and Functional Analyses Reveal That Staphylococcus aureus Antibiotic Resistance Factor HmrA Is a Zinc-dependent Endopeptidase.
J.Biol.Chem., 286:25697-25709, 2011

PubMed Abstract: HmrA is an antibiotic resistance factor of methicillin-resistant Staphylococcus aureus. Molecular analysis of this protein revealed that it is not a muramidase or β-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 ∼170-kDa homotetrameric complex of 125 Å. All four active sites are fully accessible and ∼50-70 Å 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 β-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.

PubMed: 21622555
DOI: 10.1074/jbc.M111.247437

実験手法

X-RAY DIFFRACTION (2.7 Å)