title: Cold-active enzymes studied by comparative molecular dynamics simulation.
abstract: Enzymes from cold-adapted species are significantly more active at low temperatures, even those close to zero Celsius, but the rationale of this adaptation is complex and relatively poorly understood. It is commonly stated that there is a relationship between the flexibility of an enzyme and its catalytic activity at low temperature. This paper gives the results of a study using molecular dynamics simulations performed for five pairs of enzymes, each pair comprising a cold-active enzyme plus its mesophilic or thermophilic counterpart. The enzyme pairs included alpha-amylase, citrate synthase, malate dehydrogenase, alkaline protease and xylanase. Numerous sites with elevated flexibility were observed in all enzymes; however, differences in flexibilities were not striking. Nevertheless, amino acid residues common in both enzymes of a pair (not present in insertions of a structure alignment) are generally more flexible in the cold-active enzymes. The further application of principle component analysis to the protein dynamics revealed that there are differences in the rate and/or extent of opening and closing of the active sites. The results indicate that protein dynamics play an important role in catalytic processes where structural rearrangements, such as those required for active site access by substrate, are involved. They also support the notion that cold adaptation may have evolved by selective changes in regions of enzyme structure rather than in global change to the whole protein.
authors.affiliation: Department of Biochemistry and Microbiology, Institute of Chemical Technology Prague, Technická 5, Prague 6, 166 28, Czech Republic. spiwokv@vscht.cz
authors.forename: Vojtech
authors.initials: V
authors.lastname: Spiwok
authors.forename: Petra
authors.initials: P
authors.lastname: Lipovová
authors.forename: Tereza
authors.initials: T
authors.lastname: Skálová
authors.forename: Jarmila
authors.initials: J
authors.lastname: Dusková
authors.forename: Jan
authors.initials: J
authors.lastname: Dohnálek
authors.forename: Jindrich
authors.initials: J
authors.lastname: Hasek
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Russell
authors.forename: Blanka
authors.initials: B
authors.lastname: Králová
mesh_terms: D000681:Amylases / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry; D002950:Citrate (si)-Synthase / Q000737:chemistry; D003080:Cold Temperature; D003198:Computer Simulation; D043364:Endo-1,4-beta Xylanases / Q000737:chemistry; D010450:Endopeptidases / Q000737:chemistry; D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism; D008291:Malate Dehydrogenase / Q000737:chemistry; D008958:Models, Molecular; D017433:Protein Structure, Secondary
chemical_list: D001426:Bacterial Proteins; D004798:Enzymes; D008291:Malate Dehydrogenase; D002950:Citrate (si)-Synthase; D000681:Amylases; D043364:Endo-1,4-beta Xylanases; D010450:Endopeptidases; C087822:alkaline protease