1nnr
From Proteopedia
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|PDB= 1nnr |SIZE=350|CAPTION= <scene name='initialview01'>1nnr</scene>, resolution 2.25Å | |PDB= 1nnr |SIZE=350|CAPTION= <scene name='initialview01'>1nnr</scene>, resolution 2.25Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene> | + | |LIGAND= <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Glutathione_transferase Glutathione transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.18 2.5.1.18] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Glutathione_transferase Glutathione transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.18 2.5.1.18] </span> |
|GENE= PA1129 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=208964 Pseudomonas aeruginosa PAO1]) | |GENE= PA1129 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=208964 Pseudomonas aeruginosa PAO1]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1nki|1NKI]], [[1lqk|1LQK]], [[1lqo|1LQO]], [[1lqp|1LQP]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1nnr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nnr OCA], [http://www.ebi.ac.uk/pdbsum/1nnr PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1nnr RCSB]</span> | ||
}} | }} | ||
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[[Category: Pharris, R E.]] | [[Category: Pharris, R E.]] | ||
[[Category: Rife, C L.]] | [[Category: Rife, C L.]] | ||
| - | [[Category: MN]] | ||
| - | [[Category: SO4]] | ||
[[Category: manganese binding]] | [[Category: manganese binding]] | ||
[[Category: potassium binding loop]] | [[Category: potassium binding loop]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:32:56 2008'' |
Revision as of 19:32, 30 March 2008
| |||||||
| , resolution 2.25Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | PA1129 (Pseudomonas aeruginosa PAO1) | ||||||
| Activity: | Glutathione transferase, with EC number 2.5.1.18 | ||||||
| Related: | 1NKI, 1LQK, 1LQO, 1LQP
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of a probable fosfomycin resistance protein (PA1129) from Pseudomonas aeruginosa with sulfate present in the active site
Overview
Fosfomycin [(1R,2S)-epoxypropylphosphonic acid] is a simple phosphonate found to have antibacterial activity against both Gram-positive and Gram-negative microorganisms. Early resistance to the clinical use of the antibiotic was linked to a plasmid-encoded resistance protein, FosA, that catalyzes the addition of glutathione to the oxirane ring, rendering the antibiotic inactive. Subsequent studies led to the discovery of a genomically encoded homologue in the pathogen Pseudomonas aeruginosa. The proteins are Mn(II)-dependent enzymes where the metal is proposed to act as a Lewis acid stabilizing the negative charge that develops on the oxirane oxygen in the transition state. Several simple phosphonates, including the antiviral compound phosphonoformate (K(i) = 0.4 +/- 0.1 microM, K(d) approximately 0.2 microM), are shown to be inhibitors of FosA. The crystal structure of FosA from P. aeruginosa with phosphonoformate bound in the active site has been determined at 0.95 A resolution and reveals that the inhibitor forms a five-coordinate complex with the Mn(II) center with a geometry similar to that proposed for the transition state of the reaction. Binding studies show that phosphonoformate has a near-diffusion-controlled on rate (k(on) approximately 10(7)-10(8) M(-1) s(-1)) and an off rate (k(off) = 5 s(-1)) that is slower than that for fosfomycin (k(off) = 30 s(-1)). Taken together, these data suggest that the FosA-catalyzed reaction has a very early transition state and phosphonoformate acts as a minimal transition state analogue inhibitor.
About this Structure
1NNR is a Single protein structure of sequence from Pseudomonas aeruginosa pao1. Full crystallographic information is available from OCA.
Reference
Phosphonoformate: a minimal transition state analogue inhibitor of the fosfomycin resistance protein, FosA., Rigsby RE, Rife CL, Fillgrove KL, Newcomer ME, Armstrong RN, Biochemistry. 2004 Nov 2;43(43):13666-73. PMID:15504029
Page seeded by OCA on Sun Mar 30 22:32:56 2008
