6CQS
Sediminispirochaeta smaragdinae SPS-1 metallo-beta-lactamase
Summary for 6CQS
| Entry DOI | 10.2210/pdb6cqs/pdb |
| Descriptor | Beta-lactamase, ZINC ION (3 entities in total) |
| Functional Keywords | metallo-beta-lactamase, zinc binding protein, hydrolase |
| Biological source | Sediminispirochaeta smaragdinae (strain DSM 11293 / JCM 15392 / SEBR 4228) (Spirochaeta smaragdinae) |
| Total number of polymer chains | 1 |
| Total formula weight | 27876.44 |
| Authors | Page, R.C.,VanPelt, J.,Cheng, Z.,Crowder, M.W. (deposition date: 2018-03-16, release date: 2018-08-29, Last modification date: 2023-10-04) |
| Primary citation | Cheng, Z.,VanPelt, J.,Bergstrom, A.,Bethel, C.,Katko, A.,Miller, C.,Mason, K.,Cumming, E.,Zhang, H.,Kimble, R.L.,Fullington, S.,Bretz, S.L.,Nix, J.C.,Bonomo, R.A.,Tierney, D.L.,Page, R.C.,Crowder, M.W. A Noncanonical Metal Center Drives the Activity of the Sediminispirochaeta smaragdinae Metallo-beta-lactamase SPS-1. Biochemistry, 57:5218-5229, 2018 Cited by PubMed Abstract: In an effort to evaluate whether a recently reported putative metallo-β-lactamase (MβL) contains a novel MβL active site, SPS-1 from Sediminispirochaeta smaragdinae was overexpressed, purified, and characterized using spectroscopic and crystallographic studies. Metal analyses demonstrate that recombinant SPS-1 binds nearly 2 equiv of Zn(II), and steady-state kinetic studies show that the enzyme hydrolyzes carbapenems and certain cephalosporins but not β-lactam substrates with bulky substituents at the 6/7 position. Spectroscopic studies of Co(II)-substituted SPS-1 suggest a novel metal center in SPS-1, with a reduced level of spin coupling between the metal ions and a novel Zn metal binding site. This site was confirmed with a crystal structure of the enzyme. The structure shows a Zn site that is similar to that in NDM-1 and other subclass B1 MβLs; however, the Zn metal ion is coordinated by two histidine residues and a water molecule, which is held in position by a hydrogen bond network. The Zn metal is displaced nearly 1 Å from the position reported in other MβLs. The structure also shows extended helices above the active site, which create a binding pocket that precludes the binding of substrates with large, bulky substituents at the 6/7 position of β-lactam antibiotics. This study reveals a novel metal binding site in MβLs and suggests that the targeting of metal binding sites in MβLs with inhibitors is now more challenging with the identification of this new MβL. PubMed: 30106565DOI: 10.1021/acs.biochem.8b00728 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.7 Å) |
Structure validation
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