%0 Journal Article %1 murphy_biochemical_2003 %A Murphy, Tanya A %A Simm, Alan M %A Toleman, Mark A %A Jones, Ronald N %A Walsh, Timothy R %D 2003 %J Antimicrobial Agents and Chemotherapy %K Acid Agents, Amino Pseudomonas Sequence, aeruginosa {Anti-Bacterial} {beta-Lactamases,} {beta-Lactams,} %N 2 %P 582--7 %R PMC151762 %T Biochemical characterization of the acquired metallo-beta-lactamase SPM-1 from Pseudomonas aeruginosa %U http://www.ncbi.nlm.nih.gov/pubmed/12543663 %V 47 %X SPM-1 is a new metallo-beta-lactamase recently identified in Pseudomonas aeruginosa strain 48-1997A, isolated in Sao Paulo, Brazil. Kinetic analysis demonstrated that SPM-1 has a broad hydrolytic profile across a wide range of beta-lactam antibiotics. Considerable variation was observed within the penicillin, cephalosporin, and carbapenem subfamilies; however, on the whole, SPM-1 appears to preferentially hydrolyze cephalosporins. The highest k(cat/)K(m) ratios (in micromolar per second) overall were observed for this subgroup. The hydrolytic profile of SPM-1 bears the most similarity to that of the metallo-beta-lactamase IMP-1, yet for the most part, SPM-1 has k(cat)/K(m) values higher than those of IMP-1. Zinc chelator studies established that progressive inhibition of SPM-1 by EDTA, dipicolinic acid, and 1-10-o-phenanthroline demonstrated a biexponential pattern in which none of the chelators completely inhibited SPM-1. A homology model of SPM-1 was developed on the basis of the IMP-1 crystal structure, which showed the protein folding and active-site structure characteristic of metallo-beta-lactamases and which provides an explanation for the kinetic profiles observed.

@article{murphy_biochemical_2003, abstract = {{SPM-1} is a new metallo-beta-lactamase recently identified in Pseudomonas aeruginosa strain {48-1997A,} isolated in Sao Paulo, Brazil. Kinetic analysis demonstrated that {SPM-1} has a broad hydrolytic profile across a wide range of beta-lactam antibiotics. Considerable variation was observed within the penicillin, cephalosporin, and carbapenem subfamilies; however, on the whole, {SPM-1} appears to preferentially hydrolyze cephalosporins. The highest {k(cat/)K(m)} ratios (in micromolar per second) overall were observed for this subgroup. The hydrolytic profile of {SPM-1} bears the most similarity to that of the metallo-beta-lactamase {IMP-1,} yet for the most part, {SPM-1} has {k(cat)/K(m)} values higher than those of {IMP-1.} Zinc chelator studies established that progressive inhibition of {SPM-1} by {EDTA,} dipicolinic acid, and 1-10-o-phenanthroline demonstrated a biexponential pattern in which none of the chelators completely inhibited {SPM-1.} A homology model of {SPM-1} was developed on the basis of the {IMP-1} crystal structure, which showed the protein folding and active-site structure characteristic of metallo-beta-lactamases and which provides an explanation for the kinetic profiles observed.}, added-at = {2011-03-11T10:05:34.000+0100}, author = {Murphy, Tanya A and Simm, Alan M and Toleman, Mark A and Jones, Ronald N and Walsh, Timothy R}, biburl = {https://www.bibsonomy.org/bibtex/2754b17b3b0616fa6ac430f5d3bfc93a2/jelias}, doi = {PMC151762}, interhash = {92b225ef2b820e20139e594d4d66138b}, intrahash = {754b17b3b0616fa6ac430f5d3bfc93a2}, issn = {0066-4804}, journal = {Antimicrobial Agents and Chemotherapy}, keywords = {Acid Agents, Amino Pseudomonas Sequence, aeruginosa {Anti-Bacterial} {beta-Lactamases,} {beta-Lactams,}}, month = feb, note = {{PMID:} 12543663}, number = 2, pages = {582--7}, timestamp = {2011-03-11T10:05:52.000+0100}, title = {Biochemical characterization of the acquired metallo-beta-lactamase {SPM-1} from Pseudomonas aeruginosa}, url = {http://www.ncbi.nlm.nih.gov/pubmed/12543663}, volume = 47, year = 2003 }