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1hjf
From Proteopedia
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| - | [[Image:1hjf.gif|left|200px]] | + | [[Image:1hjf.gif|left|200px]] |
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| - | '''ALTERATION OF THE CO-SUBSTRATE SELECTIVITY OF DEACETOXYCEPHALOSPORIN C SYNTHASE: THE ROLE OF ARGININE-258''' | + | {{Structure |
| + | |PDB= 1hjf |SIZE=350|CAPTION= <scene name='initialview01'>1hjf</scene>, resolution 1.60Å | ||
| + | |SITE= <scene name='pdbsite=COI:Coi+Binding+Site+For+Chain+A'>COI</scene> and <scene name='pdbsite=FE:Protein+Fe-Binding+Ligands.+2-Oxo-4-Methylpentanoate+Cos+...'>FE</scene> | ||
| + | |LIGAND= <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene> and <scene name='pdbligand=COI:2-OXO-4-METHYLPENTANOIC ACID'>COI</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= CEFE, R258Q MUTANT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1901 Streptomyces clavuligerus]) | ||
| + | }} | ||
| + | |||
| + | '''ALTERATION OF THE CO-SUBSTRATE SELECTIVITY OF DEACETOXYCEPHALOSPORIN C SYNTHASE: THE ROLE OF ARGININE-258''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1HJF is a [ | + | 1HJF is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Streptomyces_clavuligerus Streptomyces clavuligerus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HJF OCA]. |
==Reference== | ==Reference== | ||
| - | Alteration of the co-substrate selectivity of deacetoxycephalosporin C synthase. The role of arginine 258., Lee HJ, Lloyd MD, Clifton IJ, Harlos K, Dubus A, Baldwin JE, Frere JM, Schofield CJ, J Biol Chem. 2001 May 25;276(21):18290-5. Epub 2001 Feb 21. PMID:[http:// | + | Alteration of the co-substrate selectivity of deacetoxycephalosporin C synthase. The role of arginine 258., Lee HJ, Lloyd MD, Clifton IJ, Harlos K, Dubus A, Baldwin JE, Frere JM, Schofield CJ, J Biol Chem. 2001 May 25;276(21):18290-5. Epub 2001 Feb 21. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11279000 11279000] |
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Streptomyces clavuligerus]] | [[Category: Streptomyces clavuligerus]] | ||
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[[Category: FE2]] | [[Category: FE2]] | ||
[[Category: 2-oxoglutarate-dependent oxygenase]] | [[Category: 2-oxoglutarate-dependent oxygenase]] | ||
| - | [[Category: alternative 2- | + | [[Category: alternative 2-oxoacid]] |
[[Category: cephem antibiotic biosynthesis]] | [[Category: cephem antibiotic biosynthesis]] | ||
[[Category: chemical cosubstrate rescue]] | [[Category: chemical cosubstrate rescue]] | ||
[[Category: co-substrate selectivity]] | [[Category: co-substrate selectivity]] | ||
| - | ''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 11:37:50 2008'' |
Revision as of 09:37, 20 March 2008
| |||||||
| , resolution 1.60Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | and | ||||||
| Ligands: | and | ||||||
| Gene: | CEFE, R258Q MUTANT (Streptomyces clavuligerus) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
ALTERATION OF THE CO-SUBSTRATE SELECTIVITY OF DEACETOXYCEPHALOSPORIN C SYNTHASE: THE ROLE OF ARGININE-258
Overview
Deacetoxycephalosporin C synthase is an iron(II) 2-oxoglutaratedependent oxygenase that catalyzes the oxidative ring-expansion of penicillin N to deacetoxycephalosporin C. The wild-type enzyme is only able to efficiently utilize 2-oxoglutarate and 2-oxoadipate as a 2-oxoacid co-substrate. Mutation of arginine 258, the side chain of which forms an electrostatic interaction with the 5-carboxylate of the 2-oxoglutarate co-substrate, to a glutamine residue reduced activity to about 5% of the wild-type enzyme with 2-oxoglutarate. However, other aliphatic 2-oxoacids, which were not co-substrates for the wild-type enzyme, were utilized by the R258Q mutant. These 2-oxoacids "rescued" catalytic activity to the level observed for the wild-type enzyme as judged by penicillin N and G conversion. These co-substrates underwent oxidative decarboxylation as observed for 2-oxoglutarate in the normal reaction with the wild-type enzyme. Crystal structures of the iron(II)- 2-oxo-3-methylbutanoate (1.5 A), and iron(II)-2-oxo-4-methylpentanoate (1.6 A) enzyme complexes were obtained, which reveal the molecular basis for this "chemical co-substrate rescue" and help to rationalize the co-substrate selectivity of 2-oxoglutaratedependent oxygenases.
About this Structure
1HJF is a Single protein structure of sequence from Streptomyces clavuligerus. Full crystallographic information is available from OCA.
Reference
Alteration of the co-substrate selectivity of deacetoxycephalosporin C synthase. The role of arginine 258., Lee HJ, Lloyd MD, Clifton IJ, Harlos K, Dubus A, Baldwin JE, Frere JM, Schofield CJ, J Biol Chem. 2001 May 25;276(21):18290-5. Epub 2001 Feb 21. PMID:11279000
Page seeded by OCA on Thu Mar 20 11:37:50 2008
Categories: Single protein | Streptomyces clavuligerus | Baldwin, J E. | Clifton, I J. | Dubus, A. | Frere, J M. | Harlos, K. | Lee, H J. | Lloyd, M D. | Schofield, C J. | COI | FE2 | 2-oxoglutarate-dependent oxygenase | Alternative 2-oxoacid | Cephem antibiotic biosynthesis | Chemical cosubstrate rescue | Co-substrate selectivity
