The crystal structure of the Y140F mutant of ADP-L-glycero-D-manno-heptose 6-epimerase bound to ADP-beta-D-mannose suggests a one base mechanism.
Bacteria synthesize a wide array of unusual carbohydrate molecules, which they use in a variety of ways. The carbohydrate L-glycero-D-manno-heptose is an important component of lipopolysaccharide and is synthesized in a complex series of enzymatic steps. One step involves the epimerization at the C6'' position converting ADP-D-glycero-D-manno-heptose into ADP-L-glycero-D-manno-heptose. The enzyme responsible is a member of the short chain dehydrogenase superfamily, known as ADP-L-glycero-D-manno-heptose 6-epimerase (AGME). The structure of the enzyme was known but the arrangement of the catalytic site with respect to the substrate is unclear. We now report the structure of AGME bound to a substrate mimic, ADP-beta-D-mannose, which has the same stereochemical configuration as the substrate. The complex identifies the key residues and allows mechanistic insight into this novel enzyme.
Kowatz
Thomas
T
Biomolecular Sciences Research Complex, The University of St Andrews, Fife KY16 9RH, United Kingdom.
Morrison
James P
JP
Tanner
Martin E
ME
Naismith
James H
JH
D000247:Adenosine Diphosphate Sugars / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics; D002238:Carbohydrate Epimerases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020134:Catalytic Domain / Q000235:genetics; D018360:Crystallography, X-Ray / Q000379:methods*; D006539:Heptoses / Q000378:metabolism; D009154:Mutation; D017433:Protein Structure, Secondary
D000247:Adenosine Diphosphate Sugars; D006539:Heptoses; C406809:adenosine diphosphate-mannose; C026312:glycero-manno-heptose; C037213:ADP-L-glycero-D-mannoheptose-6-epimerase; D002238:Carbohydrate Epimerases