Matches in SemOpenAlex for { <https://semopenalex.org/work/W2106986901> ?p ?o ?g. }
- W2106986901 endingPage "4353" @default.
- W2106986901 startingPage "4341" @default.
- W2106986901 abstract "ABSTRACT Metallo-β-lactamase (MBL) genes confer resistance to virtually all β-lactam antibiotics and are rapidly disseminated by mobile genetic elements in Gram-negative bacteria. MBLs belong to three different subgroups, B1, B2, and B3, with the mobile MBLs largely confined to subgroup B1. The B3 MBLs are a divergent subgroup of predominantly chromosomally encoded enzymes. AIM-1 ( A delaide IM ipenmase 1) from Pseudomonas aeruginosa was the first B3 MBL to be identified on a readily mobile genetic element. Here we present the crystal structure of AIM-1 and use in silico docking and quantum mechanics and molecular mechanics (QM/MM) calculations, together with site-directed mutagenesis, to investigate its interaction with β-lactams. AIM-1 adopts the characteristic αβ/βα sandwich fold of MBLs but differs from other B3 enzymes in the conformation of an active site loop (residues 156 to 162) which is involved both in disulfide bond formation and, we suggest, interaction with substrates. The structure, together with docking and QM/MM calculations, indicates that the AIM-1 substrate binding site is narrower and more restricted than those of other B3 MBLs, possibly explaining its higher catalytic efficiency. The location of Gln157 adjacent to the AIM-1 zinc center suggests a role in drug binding that is supported by our in silico studies. However, replacement of this residue by either Asn or Ala resulted in only modest reductions in AIM-1 activity against the majority of β-lactam substrates, indicating that this function is nonessential. Our study reveals AIM-1 to be a subclass B3 MBL with novel structural and mechanistic features." @default.
- W2106986901 created "2016-06-24" @default.
- W2106986901 creator A5001917936 @default.
- W2106986901 creator A5006479516 @default.
- W2106986901 creator A5023795382 @default.
- W2106986901 creator A5030869812 @default.
- W2106986901 creator A5037611984 @default.
- W2106986901 creator A5061287131 @default.
- W2106986901 creator A5081971614 @default.
- W2106986901 date "2012-08-01" @default.
- W2106986901 modified "2023-10-10" @default.
- W2106986901 title "Crystal Structure of the Mobile Metallo-β-Lactamase AIM-1 from Pseudomonas aeruginosa: Insights into Antibiotic Binding and the Role of Gln157" @default.
- W2106986901 cites W1966182479 @default.
- W2106986901 cites W1966489440 @default.
- W2106986901 cites W1968147610 @default.
- W2106986901 cites W1969424096 @default.
- W2106986901 cites W1972009662 @default.
- W2106986901 cites W1973191530 @default.
- W2106986901 cites W1976996080 @default.
- W2106986901 cites W1977900754 @default.
- W2106986901 cites W1979054003 @default.
- W2106986901 cites W1981335245 @default.
- W2106986901 cites W1985629904 @default.
- W2106986901 cites W1994144563 @default.
- W2106986901 cites W1995725336 @default.
- W2106986901 cites W1999590520 @default.
- W2106986901 cites W2000840258 @default.
- W2106986901 cites W2001641653 @default.
- W2106986901 cites W2005600183 @default.
- W2106986901 cites W2016021368 @default.
- W2106986901 cites W2016662547 @default.
- W2106986901 cites W2018300096 @default.
- W2106986901 cites W2020276026 @default.
- W2106986901 cites W2021661744 @default.
- W2106986901 cites W2022726996 @default.
- W2106986901 cites W2023428631 @default.
- W2106986901 cites W2023692212 @default.
- W2106986901 cites W2031165491 @default.
- W2106986901 cites W2034446574 @default.
- W2106986901 cites W2036354483 @default.
- W2106986901 cites W2040651669 @default.
- W2106986901 cites W2046501778 @default.
- W2106986901 cites W2046855998 @default.
- W2106986901 cites W2048846412 @default.
- W2106986901 cites W2050384005 @default.
- W2106986901 cites W2051381895 @default.
- W2106986901 cites W2071157096 @default.
- W2106986901 cites W2073685729 @default.
- W2106986901 cites W2075745942 @default.
- W2106986901 cites W2084421339 @default.
- W2106986901 cites W2090133370 @default.
- W2106986901 cites W2090412900 @default.
- W2106986901 cites W2097527848 @default.
- W2106986901 cites W2103612221 @default.
- W2106986901 cites W2105046535 @default.
- W2106986901 cites W2106844014 @default.
- W2106986901 cites W2107326708 @default.
- W2106986901 cites W2108091863 @default.
- W2106986901 cites W2110562802 @default.
- W2106986901 cites W2111689842 @default.
- W2106986901 cites W2113416980 @default.
- W2106986901 cites W2142680296 @default.
- W2106986901 cites W2144081223 @default.
- W2106986901 cites W2150239873 @default.
- W2106986901 cites W2152885698 @default.
- W2106986901 cites W2155785227 @default.
- W2106986901 cites W2161064937 @default.
- W2106986901 cites W2161475887 @default.
- W2106986901 cites W2163341755 @default.
- W2106986901 cites W2164310491 @default.
- W2106986901 cites W2164383895 @default.
- W2106986901 cites W2171000901 @default.
- W2106986901 cites W2216839678 @default.
- W2106986901 cites W2342468449 @default.
- W2106986901 doi "https://doi.org/10.1128/aac.00448-12" @default.
- W2106986901 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3421596" @default.
- W2106986901 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22664968" @default.
- W2106986901 hasPublicationYear "2012" @default.
- W2106986901 type Work @default.
- W2106986901 sameAs 2106986901 @default.
- W2106986901 citedByCount "58" @default.
- W2106986901 countsByYear W21069869012012 @default.
- W2106986901 countsByYear W21069869012013 @default.
- W2106986901 countsByYear W21069869012014 @default.
- W2106986901 countsByYear W21069869012015 @default.
- W2106986901 countsByYear W21069869012016 @default.
- W2106986901 countsByYear W21069869012017 @default.
- W2106986901 countsByYear W21069869012018 @default.
- W2106986901 countsByYear W21069869012019 @default.
- W2106986901 countsByYear W21069869012020 @default.
- W2106986901 countsByYear W21069869012021 @default.
- W2106986901 countsByYear W21069869012022 @default.
- W2106986901 countsByYear W21069869012023 @default.
- W2106986901 crossrefType "journal-article" @default.
- W2106986901 hasAuthorship W2106986901A5001917936 @default.
- W2106986901 hasAuthorship W2106986901A5006479516 @default.
- W2106986901 hasAuthorship W2106986901A5023795382 @default.
- W2106986901 hasAuthorship W2106986901A5030869812 @default.