Linked Life Data

15829343

Source:http://linkedlifedata.com/resource/pubmed/id/15829343

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
2005-4-14
pubmed:abstractText
A computational study using some molecular modeling and quantum mechanical methods has been performed for determining the most favor activation process for Ser70 in the acylation mechanism for the cephalosporin antibiotics among the three proposed ones given in the literature. The computation is based on an X-ray structure of the B chain of the Bacillus licheniformis BS3 beta-lactamase-cefoxitin complex. The position of a catalytic water involved in one of the reaction mechanism is defined using the Grid20 and InsightII programs, while that of the truncated ligand is defined using the InsightII and FirstDiscovery programs. The geometry of structures of each reaction scheme is optimized at the HF/3-21 G level of theory, and then the single point energy for each reactive species in each reaction scheme is computed at the levels of HF/6-31 + G (3df, 2p) and B3LYP/6-31 + G (3df, 2p). The effect of solvent on each reaction scheme is also studied by comparing the calculation results for each reaction scheme either in gas phase or in solution using the HF/6-31 + G (3df, 2p) level of theory. A computation using the B3LYP/6-31 + G (3df, 2p) level of theory and the Polarized Continuum Model (PCM) and by treating water as a solvent is also conducted for each activation process. It is found that, energetically, the most favor activation process for Ser70 in the acylation mechanism is the one where a proton transfer is mediated by the catalytic water and the catalytic residues Glu166 and Ser70. This agrees with those observed in an ultrahigh resolution X-ray structure and a QM/MM theoretical study published recently on the same acylation process.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0301-4622
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
114
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
103-13
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
A theoretical study on the activation of Ser70 in the acylation mechanism of cephalosporin antibiotics.
pubmed:affiliation
Institute of Molecular Medicine and Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't