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Active‐site α‐helix in papain and the stability of the ion pair RS − ··· ImH + . Ab initio molecular orbital study
Author(s) -
van Duijnen P. Th.,
Thole B. Th.,
Broer Ria,
Nieuwpoort W. C.
Publication year - 1980
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.560170407
Subject(s) - methanethiol , chemistry , ab initio , imidazole , formamide , active site , ab initio quantum chemistry methods , helix (gastropod) , ion , computational chemistry , molecular orbital , crystallography , stereochemistry , catalysis , sulfur , molecule , organic chemistry , ecology , snail , biology
Ab initio MO calculations, using both minimal ( STO ‐3G) and extended (Roos–Siegbahn) basis sets are reported for the systems methanethiol–imidazole, methanethiol–imidazole–formaldehyde, and methanethiol–imidazole–formamide, which, together with a point‐change representation of a long α‐helix, form models for the active site of papain. It is shown that the large electric field exerted by the helix in the active‐site region is responsible for the presence of the essential residues Cys 25 and His 159 in the form of an ion pair RS − ··· ImH + , which is crucial for a recently proposed mechanism for the catalytic action of the enzyme. Also, an explanation is given for the anomalies in measured p K values for these residues. Detailed studies on the (sub)systems show that minimal basis sets lack the flexibility necessary for describing the type of proton transfer involved. We conclude that α‐helices are essential parts of enzymes and that they play a significant role in the catalytic process.