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Density functional studies on herpes simplex virus type 1 thymidine kinase-substrate interactions: the role of Tyr-172 and Met-128 in thymine fixation.

F Alber·O Kuonen·L Scapozza·G Folkers·P Carloni
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Abstract

The enzyme herpes simplex virus type 1 thymidine kinase (HSV1 TK) salvages thymidine into the DNA metabolism of the virus. In the active site, the thymine ring of the nucleoside binds in a pocket, formed by two residues, Tyr-172 and Met-128, in a sandwich-type orientation. To investigate the nature of the thymine-enzyme pocket interactions, we have carried out density functional theory calculations with gradient-corrected exchange-correlation functionals of models of the thymine-HSV1 TK adduct. Our calculations indicate that the role of Met-128 in the substrate fixation is purely steric and hydrophobic, while the substrate-Tyr-172 interaction is essentially electrostatic in nature. These findings are completely consistent with the available catalytic properties of mutants on the 128 position.

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Adenosine TriphosphateBinding SitesComputer SimulationHydrogen BondingMethionineModels, MolecularSimplexvirusStatic ElectricityThymidineThymidine KinaseTyrosineViral ProteinsComparative StudyJournal Article

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F Alber, O Kuonen, L Scapozza, G Folkers, P Carloni. 1998-06-01. Density functional studies on herpes simplex virus type 1 thymidine kinase-substrate interactions: the role of Tyr-172 and Met-128 in thymine fixation.. https://doi.org/10.1002/(sici)1097-0134(19980601)31%3A4%3C453%3A%3Aaid-prot11%3E3.0.co%3B2-e

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