Catalytic mechanism of the metal-dependent fuculose aldolase from Escherichia coli as derived from the structure.
The structure of L-fuculose-1-phosphate aldolase in a cubic crystal form has been determined with and without the inhibitor phosphoglycolohydroxamate at 2.4 and 2.7 angstrom (1 angstrom = 0.1 nm) resolution, respectively. This inhibitor mimics the enediolate transition state of the substrate moiety dihydroxyacetone phosphate. The structures showed that dihydroxyacetone phosphate ligates the zinc ion of this metal-dependent class II aldolase with its hydroxyl and keto oxygen atoms, shifting Glu73 away from the zinc coordination sphere to a non-polar environment. At this position Glu73 accepts a proton in the initial reaction step, producing the enediolate which is then stabilized by the zinc ion. The other substrate moiety L-lactaldehyde was modeled, because no binding structure is yet available.
Dreyer
M K
MK
Institut für Organische Chemie und Biochemie, Albert-Ludwigs-Universität, Freiburg im Breisgau, Germany.
Schulz
G E
GE
D000446:Aldehyde-Lyases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D018360:Crystallography, X-Ray / Q000379:methods; D004926:Escherichia coli / Q000201:enzymology*; D006877:Hydroxamic Acids / Q000378:metabolism / Q000494:pharmacology; D008954:Models, Biological; D008958:Models, Molecular; D011487:Protein Conformation
D006877:Hydroxamic Acids; C008886:phosphoglycolohydroxamate; D000446:Aldehyde-Lyases; C036027:L-fuculosephosphate aldolase