| Structural highlights
3l1v is a 2 chain structure with sequence from Ecoli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , |
| Related: | 3l1u |
| Gene: | b0200, gmhB, JW0196, yaeD (ECOLI) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[GMHB_ECOLI] Converts the D-glycero-beta-D-manno-heptose 1,7-bisphosphate intermediate into D-glycero-beta-D-manno-heptose 1-phosphate (HBP) by removing the phosphate group at the C-7 position. Also catalyzes the dephosphorylation of fructose-1,6-bisphosphate (Fru1,6bisP).[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Lipopolysaccharide is a major component of the outer membrane of gram-negative bacteria and provides a permeability barrier to many commonly used antibiotics. ADP-heptose residues are an integral part of the LPS inner core, and mutants deficient in heptose biosynthesis demonstrate increased membrane permeability. The heptose biosynthesis pathway involves phosphorylation and dephosphorylation steps not found in other pathways for the synthesis of nucleotide sugar precursors. Consequently, the heptose biosynthetic pathway has been marked as a novel target for antibiotic adjuvants, which are compounds that facilitate and potentiate antibiotic activity. D-alpha,beta-D-heptose-1,7-bisphosphate phosphatase (GmhB) catalyzes the third essential step of LPS heptose biosynthesis. This study describes the first crystal structure of GmhB and enzymatic analysis of the protein. Structure-guided mutations followed by steady state kinetic analysis, together with established precedent for HAD phosphatases, suggest that GmhB functions through a phosphoaspartate intermediate. This study provides insight into the structure-function relationship of GmhB, a new target for combatting gram-negative bacterial infection.
Structural and kinetic characterization of the LPS biosynthetic enzyme D-alpha,beta-D-heptose-1,7-bisphosphate phosphatase (GmhB) from Escherichia coli.,Taylor PL, Sugiman-Marangos S, Zhang K, Valvano MA, Wright GD, Junop MS Biochemistry. 2010 Feb 9;49(5):1033-41. PMID:20050699[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kneidinger B, Marolda C, Graninger M, Zamyatina A, McArthur F, Kosma P, Valvano MA, Messner P. Biosynthesis pathway of ADP-L-glycero-beta-D-manno-heptose in Escherichia coli. J Bacteriol. 2002 Jan;184(2):363-9. PMID:11751812
- ↑ Kuznetsova E, Proudfoot M, Gonzalez CF, Brown G, Omelchenko MV, Borozan I, Carmel L, Wolf YI, Mori H, Savchenko AV, Arrowsmith CH, Koonin EV, Edwards AM, Yakunin AF. Genome-wide analysis of substrate specificities of the Escherichia coli haloacid dehalogenase-like phosphatase family. J Biol Chem. 2006 Nov 24;281(47):36149-61. Epub 2006 Sep 21. PMID:16990279 doi:10.1074/jbc.M605449200
- ↑ Taylor PL, Sugiman-Marangos S, Zhang K, Valvano MA, Wright GD, Junop MS. Structural and kinetic characterization of the LPS biosynthetic enzyme D-alpha,beta-D-heptose-1,7-bisphosphate phosphatase (GmhB) from Escherichia coli. Biochemistry. 2010 Feb 9;49(5):1033-41. PMID:20050699 doi:10.1021/bi901780j
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