Linked Life Data

18651766

Source:http://linkedlifedata.com/resource/pubmed/id/18651766

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
33
pubmed:dateCreated
2008-8-15
pubmed:abstractText
The Escherichia coli peptide deformylase (PDF) and Bacillus thermoproteolyticus thermolysin (TLN) are two representative metal-requiring peptidases having remarkably similar active centers but distinctively different metal preferences. Zinc is a competent catalytic cofactor for TLN but not for PDF. Reaction pathways and the associated energetics for both enzymes were determined using combined semiempirical and ab initio quantum mechanical/molecular mechanical modeling, without presuming reaction coordinates. The results confirmed that both enzymes catalyze via the same chemical steps, and reproduced their different preferences for zinc or iron as competent cofactors. Further analyses indicated that different feasibility of the nucleophilic attack step leads to different metal preferences of the two enzymes. In TLN, the substrate is strongly activated and can serve as the fifth coordination ligand of zinc prior to the chemical steps. In PDF, the substrate carbonyl is activated by the chemical step itself, and becomes the fifth coordination partner of zinc only in a later stage of the nucleophilic attack. These leads to a much more difficult nucleophilic attack in PDF than in TLN. Different from some earlier suggestions, zinc has no difficulty in accepting an activated substrate as the fifth ligand to switch from tetra- to penta-coordination in either PDF or TLN. When iron replaces zinc, its stronger interaction with the hydroxide ligand may lead to higher activation barrier in TLN. In PDF, the stronger interactions of iron with ligands allow iron-substrate coordination to take place either before or at a very early stage of the chemical step, leading to effective catalysis. Our calculations also show combined semiempirical and ab initio quantum mechanical modeling can be efficient approaches to explore complicated reaction pathways in enzyme systems.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1520-6106
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
112
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10280-90
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Origins of the different metal preferences of Escherichia coli peptide deformylase and Bacillus thermoproteolyticus thermolysin: a comparative quantum mechanical/molecular mechanical study.
pubmed:affiliation
Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't