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| | <StructureSection load='1hjf' size='340' side='right'caption='[[1hjf]], [[Resolution|resolution]] 1.60Å' scene=''> | | <StructureSection load='1hjf' size='340' side='right'caption='[[1hjf]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1hjf]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/As_4.1611 As 4.1611]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HJF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1HJF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1hjf]] is a 1 chain structure with sequence from [https://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]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HJF FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=COI:2-OXO-4-METHYLPENTANOIC+ACID'>COI</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1dcs|1dcs]], [[1e5h|1e5h]], [[1e5i|1e5i]], [[1rxf|1rxf]], [[1rxg|1rxg]], [[1hjg|1hjg]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=COI:2-OXO-4-METHYLPENTANOIC+ACID'>COI</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CEFE, R258Q MUTANT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1901 AS 4.1611])</td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1hjf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hjf OCA], [https://pdbe.org/1hjf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hjf RCSB], [https://www.ebi.ac.uk/pdbsum/1hjf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hjf ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1hjf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hjf OCA], [http://pdbe.org/1hjf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1hjf RCSB], [http://www.ebi.ac.uk/pdbsum/1hjf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1hjf ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CEFE_STRC2 CEFE_STRC2]] Catalyzes the step from penicillin N to deacetoxy-cephalosporin C. | + | [https://www.uniprot.org/uniprot/CEFE_STRCL CEFE_STRCL] Catalyzes the step from penicillin N to deacetoxy-cephalosporin C. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: As 4 1611]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Baldwin, J E]] | + | [[Category: Streptomyces clavuligerus]] |
| - | [[Category: Clifton, I J]] | + | [[Category: Baldwin JE]] |
| - | [[Category: Dubus, A]] | + | [[Category: Clifton IJ]] |
| - | [[Category: Frere, J M]] | + | [[Category: Dubus A]] |
| - | [[Category: Harlos, K]] | + | [[Category: Frere JM]] |
| - | [[Category: Lee, H J]] | + | [[Category: Harlos K]] |
| - | [[Category: Lloyd, M D]] | + | [[Category: Lee HJ]] |
| - | [[Category: Schofield, C J]] | + | [[Category: Lloyd MD]] |
| - | [[Category: 2- oxoglutarate-dependent oxygenase]]
| + | [[Category: Schofield CJ]] |
| - | [[Category: Alternative 2-oxoacid]]
| + | |
| - | [[Category: Cephem antibiotic biosynthesis]]
| + | |
| - | [[Category: Chemical cosubstrate rescue]]
| + | |
| - | [[Category: Co-substrate selectivity]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Function
CEFE_STRCL Catalyzes the step from penicillin N to deacetoxy-cephalosporin C.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lee HJ, Lloyd MD, Clifton IJ, Harlos K, Dubus A, Baldwin JE, Frere JM, Schofield CJ. Alteration of the co-substrate selectivity of deacetoxycephalosporin C synthase. The role of arginine 258. J Biol Chem. 2001 May 25;276(21):18290-5. Epub 2001 Feb 21. PMID:11279000 doi:http://dx.doi.org/10.1074/jbc.M100085200
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