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1nki
From Proteopedia
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|PDB= 1nki |SIZE=350|CAPTION= <scene name='initialview01'>1nki</scene>, resolution 0.95Å | |PDB= 1nki |SIZE=350|CAPTION= <scene name='initialview01'>1nki</scene>, resolution 0.95Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene> | + | |LIGAND= <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PPF:PHOSPHONOFORMIC+ACID'>PPF</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= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1lqk|1LQK]], [[1lqo|1LQO]], [[1lqp|1LQP]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1nki FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nki OCA], [http://www.ebi.ac.uk/pdbsum/1nki PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1nki RCSB]</span> | ||
}} | }} | ||
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[[Category: Pharris, R E.]] | [[Category: Pharris, R E.]] | ||
[[Category: Rife, C L.]] | [[Category: Rife, C L.]] | ||
| - | [[Category: K]] | ||
| - | [[Category: MN]] | ||
| - | [[Category: PPF]] | ||
[[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 22:31:42 2008'' |
Revision as of 19:31, 30 March 2008
| |||||||
| , resolution 0.95Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||
| Activity: | Glutathione transferase, with EC number 2.5.1.18 | ||||||
| Related: | 1LQK, 1LQO, 1LQP
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCURE OF THE FOSFOMYCIN RESISTANCE PROTEIN A (FOSA) CONTAINING BOUND PHOSPHONOFORMATE
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
1NKI 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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