title: Rational proteomics II: electrostatic nature of cofactor preference in the short-chain oxidoreductase (SCOR) enzyme family.
abstract: The dominant role of long-range electrostatic interatomic interactions in nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NAD/NADP) cofactor recognition has been shown for enzymes of the short-chain oxidoreductase (SCOR) family. An estimation of cofactor preference based only on the contribution of the electrostatic energy term to the total energy of enzyme-cofactor interaction has been tested for approximately 40 known three-dimensional (3D) crystal complexes and approximately 330 SCOR enzymes, with cofactor preference predicted by the presence of Asp or Arg recognition residues at specific 3D positions in the beta2alpha3 loop (Duax et al., Proteins 2003;53:931-943). The results obtained were found to be consistent with approximately 90% reliable cofactor assignments for those subsets. The procedure was then applied to approximately 170 SCOR enzymes with completely uncertain NAD/NADP dependence, due to the lack of Asp and Arg marker residues. The proposed 3D electrostatic approach for cofactor assignment ("3D_DeltaE(el)") has been implemented in an automatic screening procedure, and together with the use of marker residues proposed earlier (Duax et al., Proteins 2003;53:931-943), increases the level of reliable predictions for the putative SCORs from approximately 70% to approximately 90%. It is expected to be applicable for any NAD/NADP-dependent enzyme subset having at least 25-30% sequence identity, with at least one enzyme of known 3D crystal structure.
authors.affiliation: Hauptman-Woodward Medical Research Institute and Department of Structural Biology, SUNY at Buffalo, Buffalo, New York 14203, USA.
authors.forename: Vladimir Z
authors.initials: VZ
authors.lastname: Pletnev
authors.forename: Charles M
authors.initials: CM
authors.lastname: Weeks
authors.forename: William L
authors.initials: WL
authors.lastname: Duax
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry; D001665:Binding Sites; D020134:Catalytic Domain; D018360:Crystallography, X-Ray / Q000379:methods; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D019476:Insect Proteins / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010088:Oxidoreductases / Q000737:chemistry* / Q000378:metabolism*; D010940:Plant Proteins / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D040901:Proteomics / Q000379:methods*; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; D005656:Fungal Proteins; D019476:Insect Proteins; D010940:Plant Proteins; D015800:Protozoan Proteins; D009243:NAD; D009249:NADP; D010088:Oxidoreductases