7LUU

Kinetic and Structural Characterization of the First B3 Metallo-beta-Lactamase with an Active Site Glutamic Acid

Summary for 7LUU

• Entry DOI: 10.2210/pdb7luu/pdb
• Descriptor: Subclass B3 metallo-beta-lactamase, ZINC ION, SULFATE ION, ... (5 entities in total)
• Functional Keywords: antibiotic degradation, hydrolase
• Biological source: Sphingobium indicum (strain DSM 16412 / CCM 7286 / MTCC 6364 / B90A)
• Total number of polymer chains: 1
• Total formula weight: 34804.08

Authors

Wilson, L.,Knaven, E.,Morris, M.T.,Schenk, G. (deposition date: 2021-02-23, release date: 2021-07-28, Last modification date: 2024-11-06)

Primary citation

Wilson, L.A.,Knaven, E.G.,Morris, M.T.,Monteiro Pedroso, M.,Schofield, C.J.,Bruck, T.B.,Boden, M.,Waite, D.W.,Hugenholtz, P.,Guddat, L.,Schenk, G.
Kinetic and Structural Characterization of the First B3 Metallo-beta-Lactamase with an Active-Site Glutamic Acid.
Antimicrob.Agents Chemother., 65:e0093621-e0093621, 2021

PubMed Abstract: The structural diversity in metallo-β-lactamases (MBLs), especially in the vicinity of the active site, has been a major hurdle in the development of clinically effective inhibitors. Representatives from three variants of the B3 MBL subclass, containing either the canonical HHH/DHH active-site motif (present in the majority of MBLs in this subclass) or the QHH/DHH (B3-Q) or HRH/DQK (B3-RQK) variations, were reported previously. Here, we describe the structure and kinetic properties of the first example (SIE-1) of a fourth variant containing the EHH/DHH active-site motif (B3-E). SIE-1 was identified in the hexachlorocyclohexane-degrading bacterium Sphingobium indicum, and kinetic analyses demonstrate that although it is active against a wide range of antibiotics, its efficiency is lower than that of other B3 MBLs but has increased efficiency toward cephalosporins relative to other β-lactam substrates. The overall fold of SIE-1 is characteristic of the MBLs; the notable variation is observed in the Zn1 site due to the replacement of the canonical His116 by a glutamate. The unusual preference of SIE-1 for cephalosporins and its occurrence in a widespread environmental organism suggest the scope for increased MBL-mediated β-lactam resistance. Thus, it is relevant to include SIE-1 in MBL inhibitor design studies to widen the therapeutic scope of much needed antiresistance drugs.

PubMed: 34310207
DOI: 10.1128/AAC.00936-21

Experimental method

X-RAY DIFFRACTION (1.68 Å)