Enzymes
| UniProtKB help_outline | 13,246 proteins |
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- Name help_outline D-sedoheptulose 7-phosphate Identifier CHEBI:57483 (Beilstein: 5106241) help_outline Charge -2 Formula C7H13O10P InChIKeyhelp_outline JDTUMPKOJBQPKX-GBNDHIKLSA-L SMILEShelp_outline OCC(=O)[C@@H](O)[C@H](O)[C@H](O)[C@H](O)COP([O-])([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 10 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline D-glycero-α-D-manno-heptose 7-phosphate Identifier CHEBI:60203 Charge -2 Formula C7H13O10P InChIKeyhelp_outline SDADNVAZGVDAIM-QTNLNCNHSA-L SMILEShelp_outline [H][C@@]1(O[C@H](O)[C@@H](O)[C@@H](O)[C@@H]1O)[C@H](O)COP([O-])([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 2 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline D-glycero-β-D-manno-heptose 7-phosphate Identifier CHEBI:60204 Charge -2 Formula C7H13O10P InChIKeyhelp_outline SDADNVAZGVDAIM-ZUHYCWGWSA-L SMILEShelp_outline [H][C@@]1(O[C@@H](O)[C@@H](O)[C@@H](O)[C@@H]1O)[C@H](O)COP([O-])([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 2 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:27489 | RHEA:27490 | RHEA:27491 | RHEA:27492 | |
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| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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Publications
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A preliminary X-ray study of sedoheptulose-7-phosphate isomerase from Burkholderia pseudomallei.
Kim M.S., Shin D.H.
Sedoheptulose-7-phosphate isomerase (GmhA) converts d-sedoheptulose 7-phosphate to d,d-heptose 7-phosphate. This is the first step in the biosynthesis pathway of NDP-heptose, which is responsible for the pleiotropic phenotype. This biosynthesis pathway is the target of inhibitors to increase the m ... >> More
Sedoheptulose-7-phosphate isomerase (GmhA) converts d-sedoheptulose 7-phosphate to d,d-heptose 7-phosphate. This is the first step in the biosynthesis pathway of NDP-heptose, which is responsible for the pleiotropic phenotype. This biosynthesis pathway is the target of inhibitors to increase the membrane permeability of Gram-negative pathogens or of adjuvants working synergistically with known antibiotics. Burkholderia pseudomallei is the causative agent of melioidosis, a seriously invasive disease in animals and humans in tropical and subtropical areas. GmhA from B. pseudomallei is one of the targets of antibiotic adjuvants for melioidosis. In this study, GmhA has been cloned, expressed, purified and crystallized. Synchrotron X-ray data were also collected to 1.9 angstrom resolution. The crystal belonged to the primitive orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 61.3, b = 84.2, c = 142.3 angstrom. A full structural determination is under way in order to provide insights into the structure- function relationships of this protein. << Less
Acta Crystallogr Sect F Struct Biol Cryst Commun 65:1110-1112(2009) [PubMed] [EuropePMC]
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Structure and function of sedoheptulose-7-phosphate isomerase, a critical enzyme for lipopolysaccharide biosynthesis and a target for antibiotic adjuvants.
Taylor P.L., Blakely K.M., de Leon G.P., Walker J.R., McArthur F., Evdokimova E., Zhang K., Valvano M.A., Wright G.D., Junop M.S.
The barrier imposed by lipopolysaccharide (LPS) in the outer membrane of Gram-negative bacteria presents a significant challenge in treatment of these organisms with otherwise effective hydrophobic antibiotics. The absence of L-glycero-D-manno-heptose in the LPS molecule is associated with a drama ... >> More
The barrier imposed by lipopolysaccharide (LPS) in the outer membrane of Gram-negative bacteria presents a significant challenge in treatment of these organisms with otherwise effective hydrophobic antibiotics. The absence of L-glycero-D-manno-heptose in the LPS molecule is associated with a dramatically increased bacterial susceptibility to hydrophobic antibiotics and thus enzymes in the ADP-heptose biosynthesis pathway are of significant interest. GmhA catalyzes the isomerization of D-sedoheptulose 7-phosphate into D-glycero-D-manno-heptose 7-phosphate, the first committed step in the formation of ADP-heptose. Here we report structures of GmhA from Escherichia coli and Pseudomonas aeruginosa in apo, substrate, and product-bound forms, which together suggest that GmhA adopts two distinct conformations during isomerization through reorganization of quaternary structure. Biochemical characterization of GmhA mutants, combined with in vivo analysis of LPS biosynthesis and novobiocin susceptibility, identifies key catalytic residues. We postulate GmhA acts through an enediol-intermediate isomerase mechanism. << Less
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The structure of sedoheptulose-7-phosphate isomerase from Burkholderia pseudomallei reveals a zinc binding site at the heart of the active site.
Harmer N.J.
Heptoses are found in the surface polysaccharides of most bacteria, contributing to structures that are essential for virulence and antibiotic resistance. Consequently, the biosynthetic enzymes for these sugars are attractive targets for novel antibiotics. The best characterized biosynthetic enzym ... >> More
Heptoses are found in the surface polysaccharides of most bacteria, contributing to structures that are essential for virulence and antibiotic resistance. Consequently, the biosynthetic enzymes for these sugars are attractive targets for novel antibiotics. The best characterized biosynthetic enzyme is GmhA, which catalyzes the conversion of sedoheptulose-7-phosphate into D-glycero-D-manno-heptopyranose-7-phosphate, the first step in the biosynthesis of heptose. Here, the structure of GmhA from Burkholderia pseudomallei is reported. This enzyme contains a zinc ion at the heart of its active site: this ion stabilizes the active, closed form of the enzyme and presents coordinating side chains as a potential acid and base to drive catalysis. A complex with the product demonstrates that the enzyme retains activity in the crystal and thus suggests that the closed conformation is catalytically relevant and is an excellent target for the development of therapeutics. A revised mechanism for the action of GmhA is postulated on the basis of this structure and the activity of B. pseudomallei GmhA mutants. << Less