Format

Send to

Choose Destination
J Biotechnol. 1997 Oct 17;58(2):89-100.

Receptor site and stereospecifity of dihydrolipoamide dehydrogenase for R- and S-lipoamide: a molecular modeling study.

Author information

1
Physiologisch-Chemisches Institut, Eberhard-Karls Universität Tübingen, Germany. h.a.bisswanger@uni-tuebingen.de

Abstract

The binding of the substrate R-dihydrolipoamide to the active site of dihydrolipoamide dehydrogenase has been investigated by molecular modeling and energy-minimization studies on the basis of the resolved 3-dimensional structure of the enzyme from Azotobacter vinelandii (PDB entry 3LAD) which was determined without its bound substrate. The binding model is used as a template for a FIELD-FIT docking procedure for the inactive S-enantiomer of dihydrolipoamide which is an inhibitor of the enzyme. Results show that only the active R-enantiomer is able to form direct contacts with the reactive thiol groups and imidazol base at the active site, whereas with the S-enantiomer the SH-group at C6 points away from the His450* base. Evaluation of the binding energy to the receptor site yields nearly the same value for both enantiomers. This is in accordance with experimental results which show that the stereospecifity of dihydrolipoamide dehydrogenase occurs more at the level of catalysis than of binding. The substrate/receptor model is extended to the binding of lipoyllysine, the substrate of dihydrolipoamide dehydrogenase, when the enzyme is integrated into the pyruvate dehydrogenase complex. The penetration-site of the lipoyllysine arm into the structure of dihydrolipoamide dehydrogenase could be identified. The consequences for the interaction of dihydrolipoamide dehydrogenase with the lipoyl domain of the alpha-oxoacid dehydrogenase complexes are discussed.

PMID:
9383983
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center