title: The stability and hydrophobicity of cytosolic and mitochondrial malate dehydrogenases and their relation to chaperonin-assisted folding.
abstract: mMDH and cMDH are structurally homologous enzymes which show very different responses to chaperonins during folding. The hydrophilic and stable cMDH is bound by cpn60 but released by Mg-ATP alone, while the hydrophobic and unstable mMDH requires both Mg-ATP and cpn10. Citrate equalises the stability of the native state of the two proteins but has no effect on the co-chaperonin requirement, implying that hydrophobicity, and not stability, is the determining factor. The yield and rate of folding of cMDH is unaffected while that of mMDH is markedly increased by the presence of cpn60, cpn10 and Mg-ATP. In 200 mM orthophosphate, chaperonins do not enhance the rate of folding of mMDH, but in low phosphate concentrations chaperonin-assisted folding is 3-4-times faster.
authors.affiliation: Department of Biochemistry, University of Bristol, School of Medical Sciences, UK.
authors.forename: R A
authors.initials: RA
authors.lastname: Staniforth
authors.forename: A
authors.initials: A
authors.lastname: Cortés
authors.forename: S G
authors.initials: SG
authors.lastname: Burston
authors.forename: T
authors.initials: T
authors.lastname: Atkinson
authors.forename: J J
authors.initials: JJ
authors.lastname: Holbrook
authors.forename: A R
authors.initials: AR
authors.lastname: Clarke
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D018833:Chaperonins; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003600:Cytosol / Q000201:enzymology*; D004795:Enzyme Stability; D004926:Escherichia coli / Q000737:chemistry; D007700:Kinetics; D008291:Malate Dehydrogenase / Q000737:chemistry* / Q000378:metabolism; D008929:Mitochondria, Heart / Q000201:enzymology*; D010710:Phosphates / Q000494:pharmacology; D011489:Protein Denaturation; D017510:Protein Folding; D011506:Proteins / Q000494:pharmacology*; D013816:Thermodynamics
chemical_list: D010710:Phosphates; D011506:Proteins; D000255:Adenosine Triphosphate; D008291:Malate Dehydrogenase; D018833:Chaperonins