Multivariant analysis of core structure in Alcohol Dehydrogenases

A progressive computational analysis of available sequence and crystal structure data was used to identify functionally and structurally important residues in medium-chain Alcohol dehydrogenases super family throughout evolution. Altman and Gretsine core finding method was used to identify a core set of atoms with low structural variability. With further analysis of core regions in ADHs (solvent exposure and number of contacts) and also sequential analysis, we could infer the common properties of highly conserved positions in ADHs. The sequential analysis was done with respect to some special properties of amino acids in order to derive the level of conservation. The core structure analysis was re-judged in light of sequential analysis. Sixty percent of the core positions correspond to the highly conserved positions that were found by the sequence analysis.It seems that the core positions in ADHs are responsible for the maintenance of structural integrity and also contribute to the active site. Location of rigid parts of structures in catalytic domain may help to minimize the thermal fluctuation effect on substrate binding and would probably keep the structure in a good condition. Our data supports that it is possible to define patterns of conservity in some important region in sequence of Alcohol dehydrogenase and explain patterns of structural stability which are necessary for overcoming throughout evolution.