caa a22 4500 605507422 CHVBK 20210128100632.0 cr unu---uuuuu 210128e20150601xx s 000 0 eng 10.1007/s00775-015-1250-x doi (NATIONALLICENCE)springer-10.1007/s00775-015-1250-x β-Lactam antibiotic-degrading enzymes from non-pathogenic marine organisms: a potential threat to human health [Elektronische Daten] [Manfredi Miraula, Jacob Whitaker, Gerhard Schenk, Nataša Mitić] Metallo-β-lactamases (MBLs) are a family of Zn(II)-dependent enzymes that inactivate most of the commonly used β-lactam antibiotics. They have emerged as a major threat to global healthcare. Recently, we identified two novel MBL-like proteins, Maynooth IMipenemase-1 (MIM-1) and Maynooth IMipenemase-2 (MIM-2), in the marine organisms Novosphingobium pentaromativorans and Simiduia agarivorans, respectively. Here, we demonstrate that MIM-1 and MIM-2 have catalytic activities comparable to those of known MBLs, but from the pH dependence of their catalytic parameters it is evident that both enzymes differ with respect to their mechanisms, with MIM-1 preferring alkaline and MIM-2 acidic conditions. Both enzymes require Zn(II) but activity can also be reconstituted with other metal ions including Co(II), Mn(II), Cu(II) and Ca(II). Importantly, the substrate preference of MIM-1 and MIM-2 appears to be influenced by their metal ion composition. Since neither N. pentaromativorans nor S. agarivorans are human pathogens, the precise biological role(s) of MIM-1 and MIM-2 remains to be established. However, due to the similarity of at least some of their in vitro functional properties to those of known MBLs, MIM-1 and MIM-2 may provide essential structural insight that may guide the design of as of yet elusive clinically useful MBL inhibitors. SBIC, 2015 Antibiotic resistance nationallicence β-Lactam antibiotics nationallicence Metallo-β-lactamase nationallicence Metallohydrolase nationallicence Catalysis nationallicence Miraula Manfredi Department of Chemistry, Maynooth University, Maynooth, Co., Kildare, Ireland aut Whitaker Jacob School of Chemistry and Molecular Biosciences, The University of Queensland, 4072, St. Lucia, QLD, Australia aut Schenk Gerhard School of Chemistry and Molecular Biosciences, The University of Queensland, 4072, St. Lucia, QLD, Australia aut Mitić Nataša Department of Chemistry, Maynooth University, Maynooth, Co., Kildare, Ireland aut JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/4(2015-06-01), 639-651 0949-8257 20:4<639 2015 20 775 https://doi.org/10.1007/s00775-015-1250-x text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00775-015-1250-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Miraula Manfredi Department of Chemistry, Maynooth University, Maynooth, Co., Kildare, Ireland aut NATIONALLICENCE 700 1- Whitaker Jacob School of Chemistry and Molecular Biosciences, The University of Queensland, 4072, St. Lucia, QLD, Australia aut NATIONALLICENCE 700 1- Schenk Gerhard School of Chemistry and Molecular Biosciences, The University of Queensland, 4072, St. Lucia, QLD, Australia aut NATIONALLICENCE 700 1- Mitić Nataša Department of Chemistry, Maynooth University, Maynooth, Co., Kildare, Ireland aut NATIONALLICENCE 773 0- JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/4(2015-06-01), 639-651 0949-8257 20:4<639 2015 20 775