Molecular dynamics study of interaction and substrate channeling between neuron-specific enolase and B-type phosphoglycerate mutase.
Phosphoglycerate mutase (PGM) and enolase are consecutive enzymes in the glycolytic pathway. We used molecular dynamics simulation to examine the interaction of human B-type PGM (dPGM-B) and neuron-specific enolase (NSE). Specifically, we studied the interactions of 31 orientations of these enzymes by means of the effective energy function implicit solvation method. Interactions between active regions of the enzymes occurred preferentially, although the strongest interactions appeared to be between the back side of NSE and the active regions of dPGM-B. Cleavage of 2PG from dPGM-B was investigated, and the Ser(14)-Leu(30) loop of dPGM-B is suggested as a cleavage site and, likely, another entrance site of a ligand. Substrate channeling between the enzymes was observed when NSE with its active regions Leu(11)-Asn(16), Arg(49)-Lys(59), and Gly(155)-Ala(158) covered the Ser(14)-Leu(30) loop of dPGM-B. Analyses of the results make us believe that the channeling between PGM and enolase "benefits" from weak interaction. The probability of formation of channeling favorable complex is estimated to be up to 5%, while functional interaction between NSE and dPGM-B might be as high as 20%. NSE and dPGM-B functional interaction seems not to be isotype specific.
Laboratory of Computer Modeling, Institute of Molecular Biology, Yerevan, Armenia.
Davit
D
Hakobyan
Karen
K
Nazaryan
D006801:Humans; D007527:Isoenzymes; D056004:Molecular Dynamics Simulation; D010736:Phosphoglycerate Mutase / Q000737:chemistry* / Q000378:metabolism*; D010751:Phosphopyruvate Hydratase / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D013816:Thermodynamics
D007527:Isoenzymes; D010751:Phosphopyruvate Hydratase; D010736:Phosphoglycerate Mutase