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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
Author(s) -
Brocklehurst Simon M.,
Perham Richard N.
Publication year - 1993
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.5560020413
Subject(s) - biotinylation , pyruvate carboxylase , cleavage (geology) , glycine , biochemistry , yeast , biotin , chemistry , domain (mathematical analysis) , computational biology , biology , enzyme , amino acid , paleontology , fracture (geology) , mathematical analysis , mathematics
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 by 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.