STRUCTURAL BIOINFORMATICS OF CBS DOMAIN

 

Vojtěch Spiwok, Olga Součková

 

Department of Biochemistry and Microbiology,Institute of Chemical Technology, Prague

Technická 3, Prague 6. 166 28, Czech Republic

 

CBS (cystathionine β-synthase) domain pair, also known as Bateman domain, is an ancient scaffold present in numerous organisms form Archaea to mammals. It regulates the function of many enzymes such as cystathionine β-synthase, AMP-activated protein kinase or inosine monophosphate dehydrogenase, as well as voltage gated chloride channels and other transporters. It can bind different nucleotide phosphates, S-adenosylmethionine, ions and other ligands. During our attempt aimed at refinement of a model of the CBS domain pair from human cystathionine β-synthase we collected and structurally aligned ~140 CBS domain pairs from ~70 experimental 3D structures of proteins containing this structure. This scaffold forms a pseudo-symmetric pair of two subdomains and this pseudo-symmetry causes that a ligand can bind either in the binding site A or B or both sites can be occupied by ligands, where sides A and B are associated by the (pseudo-)symmetry. Here we show a comparison of CBS domains in terms of their overall structure, binding sites and amino acid sequence in order allow better prediction of binding site details, prediction of the ligand, its binding mode and conformational changes associated with biological function.