Prediction of the three-dimensional structures of the biotinylated domain from yeast pyruvate carboxylase and of the lipoylated H-protein from the pea leaf glycine cleavage system: a new automated method for the prediction of protein tertiary structure.
A new, automated, knowledge-based method for the construction of three-dimensional models of proteins is described. Geometric restraints on target structures are calculated from a consideration of homologous template structures and the wider knowledge base of unrelated protein structures. Three-dimensional structures are calculated from initial partly folded states by high-temperature molecular dynamics simulations followed slow cooling of the system (simulated annealing) using nonphysical potentials. Three-dimensional models for the biotinylated domain from the pyruvate carboxylase of yeast and the lipoylated H-protein from the glycine cleavage system of pea leaf were constructed, based on the known structures of two lipoylated domains of 2-oxo acid dehydrogenase multienzyme complexes. Despite their weak sequence similarity, the three proteins are predicted to have similar three-dimensional structures, representative of a new protein module. Implications for the mechanisms of posttranslational modification of these proteins and their catalytic function are discussed.
Department of Biochemistry, University of Cambridge, United Kingdom.
S M
SM
Brocklehurst
R N
RN
Perham
D000594:Amino Acid Oxidoreductases; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry*; D007887:Fabaceae / Q000737:chemistry; D050961:Glycine Decarboxylase Complex H-Protein; D050841:Glycine Dehydrogenase (Decarboxylating); D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010946:Plants, Medicinal; D017434:Protein Structure, Tertiary; D011766:Pyruvate Carboxylase / Q000737:chemistry*; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment
D002352:Carrier Proteins; D050961:Glycine Decarboxylase Complex H-Protein; D029701:Saccharomyces cerevisiae Proteins; D000594:Amino Acid Oxidoreductases; C494237:GCV2 protein, S cerevisiae; D050841:Glycine Dehydrogenase (Decarboxylating); D011766:Pyruvate Carboxylase