Topology of human methionine S-adenosyltransferase

Abstract

Insights into the three-dimensional (3D) structure of the enzyme, Methionine <i>S</i>-adenosyltransferase (MAT), can throw light on its role in humans and help in evolving selectivity attributes of inhibitors targeted at bacterial MAT. We report here a 3D-

model of human MAT, using the X-ray structure of MAT from the rat as a template, by comparative protein modelling &nbsp;principles. The resulting model has the correct stereochemistry as gauged from the Ramachandran plot and good 3D- structure compatibility as assessed by the <i>Profiles-3D </i>score. The structurally and functionally important residues (active site) of human MAT have been identified based on information in the rat MAT crystal structure and the point mutation data reported for human MAT. The homology model does conserve the topological and active site features of the MAT family of proteins. However, there exist some differences in the molecular electrostatic potentials (MEP) of MAT from humans and <i>M. tuberculosis. </i>These differences provide a scope for achieving selectivity and specificity of mycobacterium-MAT inhibition over human MAT.