1nnr
From Proteopedia
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| - | [[Image:1nnr.gif|left|200px]] | + | [[Image:1nnr.gif|left|200px]] |
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| - | '''Crystal structure of a probable fosfomycin resistance protein (PA1129) from Pseudomonas aeruginosa with sulfate present in the active site''' | + | {{Structure |
| + | |PDB= 1nnr |SIZE=350|CAPTION= <scene name='initialview01'>1nnr</scene>, resolution 2.25Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene> and <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] | ||
| + | |GENE= PA1129 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=208964 Pseudomonas aeruginosa PAO1]) | ||
| + | }} | ||
| + | |||
| + | '''Crystal structure of a probable fosfomycin resistance protein (PA1129) from Pseudomonas aeruginosa with sulfate present in the active site''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1NNR is a [ | + | 1NNR is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_pao1 Pseudomonas aeruginosa pao1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NNR OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/15504029 15504029] |
[[Category: Glutathione transferase]] | [[Category: Glutathione transferase]] | ||
[[Category: Pseudomonas aeruginosa pao1]] | [[Category: Pseudomonas aeruginosa pao1]] | ||
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[[Category: potassium binding loop]] | [[Category: potassium binding loop]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:59:16 2008'' |
Revision as of 10:59, 20 March 2008
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| , resolution 2.25Å | |||||||
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| Ligands: | and | ||||||
| Gene: | PA1129 (Pseudomonas aeruginosa PAO1) | ||||||
| Activity: | Glutathione transferase, with EC number 2.5.1.18 | ||||||
| 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
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