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1hjg

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|PDB= 1hjg |SIZE=350|CAPTION= <scene name='initialview01'>1hjg</scene>, resolution 1.5&Aring;
|PDB= 1hjg |SIZE=350|CAPTION= <scene name='initialview01'>1hjg</scene>, resolution 1.5&Aring;
|SITE= <scene name='pdbsite=FE:Protein+Fe-Binding+Ligands.+2-Oxo-3-Methylbutanoate+Cosu+...'>FE</scene> and <scene name='pdbsite=KIV:Kiv+Binding+Site+For+Chain+A'>KIV</scene>
|SITE= <scene name='pdbsite=FE:Protein+Fe-Binding+Ligands.+2-Oxo-3-Methylbutanoate+Cosu+...'>FE</scene> and <scene name='pdbsite=KIV:Kiv+Binding+Site+For+Chain+A'>KIV</scene>
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|LIGAND= <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene> and <scene name='pdbligand=KIV:3-METHYL-2-OXOBUTANOIC ACID'>KIV</scene>
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|LIGAND= <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=KIV:3-METHYL-2-OXOBUTANOIC+ACID'>KIV</scene>
|ACTIVITY=
|ACTIVITY=
|GENE= CEFE, R258Q MUTANT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1901 Streptomyces clavuligerus])
|GENE= CEFE, R258Q MUTANT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1901 Streptomyces clavuligerus])
 +
|DOMAIN=
 +
|RELATEDENTRY=
 +
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1hjg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hjg OCA], [http://www.ebi.ac.uk/pdbsum/1hjg PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1hjg RCSB]</span>
}}
}}
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[[Category: Lloyd, M D.]]
[[Category: Lloyd, M D.]]
[[Category: Schofield, C J.]]
[[Category: Schofield, C J.]]
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[[Category: FE2]]
 
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[[Category: KIV]]
 
[[Category: 2-oxoglutarate-dependent oxygenase]]
[[Category: 2-oxoglutarate-dependent oxygenase]]
[[Category: alternative 2-oxoacid]]
[[Category: alternative 2-oxoacid]]
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[[Category: co-substrate selectivity]]
[[Category: co-substrate selectivity]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:37:50 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:06:07 2008''

Revision as of 18:06, 30 March 2008


PDB ID 1hjg

Drag the structure with the mouse to rotate
, resolution 1.5Å
Sites: and
Ligands: ,
Gene: CEFE, R258Q MUTANT (Streptomyces clavuligerus)
Resources: FirstGlance, OCA, PDBsum, RCSB
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

1HJG 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

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