AIM-1: an antibiotic-degrading metallohydrolase that displays mechanistic flexibility

Selleck, Christopher, Larrabee James A., Harmer, Jeffrey, Guddat, Luke W., Mitić, Natasa, Helweh, Waleed, Ollis, David L., Craig, Whitney R., Tierney, David L., Monteiro Pedroso, Marcelo and Schenk, Gerhard (2016) AIM-1: an antibiotic-degrading metallohydrolase that displays mechanistic flexibility. Chemistry, 22 49: 17704-17714. doi:10.1002/chem.201602762


Author Selleck, Christopher
Larrabee James A.
Harmer, Jeffrey
Guddat, Luke W.
Mitić, Natasa
Helweh, Waleed
Ollis, David L.
Craig, Whitney R.
Tierney, David L.
Monteiro Pedroso, Marcelo
Schenk, Gerhard
Title AIM-1: an antibiotic-degrading metallohydrolase that displays mechanistic flexibility
Journal name Chemistry   Check publisher's open access policy
ISSN 0947-6539
1521-3765
Publication date 2016-12-01
Year available 2016
Sub-type Article (original research)
DOI 10.1002/chem.201602762
Open Access Status Not yet assessed
Volume 22
Issue 49
Start page 17704
End page 17714
Total pages 11
Place of publication Weinheim, Germany
Publisher Wiley
Language eng
Subject 1600 Chemistry
Abstract Antibiotic resistance has emerged as a major threat to global health care. This is largely due to the fact that many pathogens have developed strategies to acquire resistance to antibiotics. Metallo-β-lactamases (MBL) have evolved to inactivate most of the commonly used β-lactam antibiotics. AIM-1 is one of only a few MBLs from the B3 subgroup that is encoded on a mobile genetic element in a major human pathogen. Here, its mechanism of action was characterised with a combination of spectroscopic and kinetic techniques and compared to that of other MBLs. Unlike other MBLs it appears that AIM-1 has two avenues available for the turnover of the substrate nitrocefin, distinguished by the identity of the rate-limiting step. This observation may be relevant with respect to inhibitor design for this group of enzymes as it demonstrates that at least some MBLs are very flexible in terms of interactions with substrates and possibly inhibitors.
Keyword Antibiotic resistance
Imipenemase
Metallo-β-lactamase
Metalloenzyme
β-lactam antibiotics
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID APP1084778
DP150104358
FT120100694
CHE1303852
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Chemistry and Molecular Biosciences
Centre for Advanced Imaging Publications
 
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Created: Thu, 10 Nov 2016, 01:19:11 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences