title: Activity and specificity of human aldolases.
abstract: The structure of the type I fructose 1,6-bisphosphate aldolase from human muscle has been extended from 3 A to 2 A resolution. The improvement in the resulting electron density map is such that the 20 or so C-terminal residues, known to be associated with activity and isozyme specificity, have been located. The side-chain of the Schiff's base-forming lysine 229 is located towards the centre of an eight-stranded beta-barrel type structure. The C-terminal "tail" extends from the rim of the beta-barrel towards lysine 229, thus forming part of the active site of the enzyme. This structural arrangement appears to explain the difference in activity and specificity of the three tissue-specific human aldolases and helps with our understanding of the type I aldolase reaction mechanism.
authors.affiliation: Department of Biochemistry, School of Medical Sciences, University of Bristol, U.K.
authors.forename: S J
authors.initials: SJ
authors.lastname: Gamblin
authors.forename: G J
authors.initials: GJ
authors.lastname: Davies
authors.forename: J M
authors.initials: JM
authors.lastname: Grimes
authors.forename: R M
authors.initials: RM
authors.lastname: Jackson
authors.forename: J A
authors.initials: JA
authors.lastname: Littlechild
authors.forename: H C
authors.initials: HC
authors.lastname: Watson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D005634:Fructose-Bisphosphate Aldolase / Q000737:chemistry* / Q000378:metabolism; D005635:Fructosediphosphates / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009132:Muscles / Q000201:enzymology; D010961:Plasmodium / Q000201:enzymology; D011487:Protein Conformation; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014345:Trypanosoma / Q000201:enzymology
chemical_list: D005635:Fructosediphosphates; D007527:Isoenzymes; D005634:Fructose-Bisphosphate Aldolase; C029063:fructose-1,6-diphosphate