Abstract:
:A molecular dynamics study was performed to compare the differences in the active-site dynamics of the wild-type and W137F mutant enzymes of 4-chlorobenzoyl-CoA dehalogenase. Only in the wild-type simulation are conformations formed between the catalytic Asp-145 and 4-chlorobenzoyl-CoA, which resemble the ab initio calculated gas-phase transition-state geometry. In the W137F simulation, the hydrogen bond formed between His-90 and Asp-145 persisted throughout the simulation, causing the carboxylate of Asp-145 to be distant from the benzoyl ring of 4-chlorobenzoyl-CoA. In both simulations, water molecules were able to diffuse into the active site of the enzymes. The trajectories provide insight into the routes that water may use to get into position for the hydrolysis portion of the dehalogenation reaction. In both simulations, the water molecule entering the active site forms a hydrogen bond with Asp-145.
journal_name
Proc Natl Acad Sci U S Aauthors
Lau EY,Bruice TCdoi
10.1073/pnas.161282698keywords:
subject
Has Abstractpub_date
2001-08-14 00:00:00pages
9527-32issue
17eissn
0027-8424issn
1091-6490pii
161282698journal_volume
98pub_type
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