2i2w
From Proteopedia
(New page: 200px<br /><applet load="2i2w" size="350" color="white" frame="true" align="right" spinBox="true" caption="2i2w, resolution 1.95Å" /> '''Crystal Structure of...) |
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caption="2i2w, resolution 1.95Å" /> | caption="2i2w, resolution 1.95Å" /> | ||
'''Crystal Structure of Escherichia Coli Phosphoheptose Isomerase'''<br /> | '''Crystal Structure of Escherichia Coli Phosphoheptose Isomerase'''<br /> | ||
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| + | ==Overview== | ||
| + | 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. | ||
==About this Structure== | ==About this Structure== | ||
| - | 2I2W is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I2W OCA]. | + | 2I2W is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Known structural/functional Site: <scene name='pdbsite=AC1:Gol Binding Site For Residue D 196'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I2W OCA]. |
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| + | ==Reference== | ||
| + | Structure and Function of Sedoheptulose-7-phosphate Isomerase, a Critical Enzyme for Lipopolysaccharide Biosynthesis and a Target for Antibiotic Adjuvants., Taylor PL, Blakely KM, de Leon GP, Walker JR, McArthur F, Evdokimova E, Zhang K, Valvano MA, Wright GD, Junop MS, J Biol Chem. 2008 Feb 1;283(5):2835-45. Epub 2007 Dec 3. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18056714 18056714] | ||
[[Category: Escherichia coli]] | [[Category: Escherichia coli]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: phosphoheptose isomerase]] | [[Category: phosphoheptose isomerase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jan 31 10:56:45 2008'' |
Revision as of 08:56, 31 January 2008
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Crystal Structure of Escherichia Coli Phosphoheptose Isomerase
Overview
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.
About this Structure
2I2W is a Single protein structure of sequence from Escherichia coli with as ligand. Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
Structure and Function of Sedoheptulose-7-phosphate Isomerase, a Critical Enzyme for Lipopolysaccharide Biosynthesis and a Target for Antibiotic Adjuvants., Taylor PL, Blakely KM, de Leon GP, Walker JR, McArthur F, Evdokimova E, Zhang K, Valvano MA, Wright GD, Junop MS, J Biol Chem. 2008 Feb 1;283(5):2835-45. Epub 2007 Dec 3. PMID:18056714
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