1nx4: Difference between revisions

Revision as of 09:29, 11 September 2015

The crystal structure of carbapenem synthase (CarC)

Structural highlights

1nx4 is a 3 chain structure with sequence from "bacillus_carotovorus"_jones_1901 "bacillus carotovorus" jones 1901. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	AKG, FE
NonStd Res:	MSE
Related:	1nx8
Gene:	CarC ("Bacillus carotovorus" Jones 1901)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[CARC_PECCC] Catalyzes the Fe(2+) and alpha-ketoglutarate-dependent conversion of (3S,5S)-carbapenam to (5R)-carbapenem, an essential step in carbapenem antibiotic biosynthesis.^[1] ^[2] ^[3] ^[4]

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

The proposed biosynthetic pathway to the carbapenem antibiotics proceeds via epimerization/desaturation of a carbapenam in an unusual process catalyzed by an iron- and 2-oxoglutarate-dependent oxygenase, CarC. Crystal structures of CarC complexed with Fe(II) and 2-oxoglutarate reveal it to be hexameric (space group C2221), consistent with solution studies. CarC monomers contain a double-stranded beta-helix core that supports ligands binding a single Fe(II) to which 2-oxoglutarate complexes in a bi-dentate manner. A structure was obtained with l-N-acetylproline acting as a substrate analogue. Quantum mechanical/molecular mechanical modeling studies with stereoisomers of carbapenams and carbapenems were used to investigate substrate binding. The combined work will stimulate further mechanistic studies and aid in the engineering of carbapenem biosynthesis.

Crystal structure of carbapenem synthase (CarC).,Clifton IJ, Doan LX, Sleeman MC, Topf M, Suzuki H, Wilmouth RC, Schofield CJ J Biol Chem. 2003 Jun 6;278(23):20843-50. Epub 2003 Feb 28. PMID:12611886^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ McGowan SJ, Sebaihia M, O'Leary S, Hardie KR, Williams P, Stewart GS, Bycroft BW, Salmond GP. Analysis of the carbapenem gene cluster of Erwinia carotovora: definition of the antibiotic biosynthetic genes and evidence for a novel beta-lactam resistance mechanism. Mol Microbiol. 1997 Nov;26(3):545-56. PMID:9402024
↑ Stapon A, Li R, Townsend CA. Carbapenem biosynthesis: confirmation of stereochemical assignments and the role of CarC in the ring stereoinversion process from L-proline. J Am Chem Soc. 2003 Jul 16;125(28):8486-93. PMID:12848554 doi:https://dx.doi.org/10.1021/ja034248a
↑ Sleeman MC, Smith P, Kellam B, Chhabra SR, Bycroft BW, Schofield CJ. Biosynthesis of carbapenem antibiotics: new carbapenam substrates for carbapenem synthase (CarC). Chembiochem. 2004 Jun 7;5(6):879-82. PMID:15174175 doi:https://dx.doi.org/10.1002/cbic.200300908
↑ Clifton IJ, Doan LX, Sleeman MC, Topf M, Suzuki H, Wilmouth RC, Schofield CJ. Crystal structure of carbapenem synthase (CarC). J Biol Chem. 2003 Jun 6;278(23):20843-50. Epub 2003 Feb 28. PMID:12611886 doi:10.1074/jbc.M213054200
↑ Clifton IJ, Doan LX, Sleeman MC, Topf M, Suzuki H, Wilmouth RC, Schofield CJ. Crystal structure of carbapenem synthase (CarC). J Biol Chem. 2003 Jun 6;278(23):20843-50. Epub 2003 Feb 28. PMID:12611886 doi:10.1074/jbc.M213054200

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] McGowan SJ, Sebaihia M, O'Leary S, Hardie KR, Williams P, Stewart GS, Bycroft BW, Salmond GP. Analysis of the carbapenem gene cluster of Erwinia carotovora: definition of the antibiotic biosynthetic genes and evidence for a novel beta-lactam resistance mechanism. Mol Microbiol. 1997 Nov;26(3):545-56. PMID:9402024

[2] Stapon A, Li R, Townsend CA. Carbapenem biosynthesis: confirmation of stereochemical assignments and the role of CarC in the ring stereoinversion process from L-proline. J Am Chem Soc. 2003 Jul 16;125(28):8486-93. PMID:12848554 doi:https://dx.doi.org/10.1021/ja034248a

[3] Sleeman MC, Smith P, Kellam B, Chhabra SR, Bycroft BW, Schofield CJ. Biosynthesis of carbapenem antibiotics: new carbapenam substrates for carbapenem synthase (CarC). Chembiochem. 2004 Jun 7;5(6):879-82. PMID:15174175 doi:https://dx.doi.org/10.1002/cbic.200300908

[4] Clifton IJ, Doan LX, Sleeman MC, Topf M, Suzuki H, Wilmouth RC, Schofield CJ. Crystal structure of carbapenem synthase (CarC). J Biol Chem. 2003 Jun 6;278(23):20843-50. Epub 2003 Feb 28. PMID:12611886 doi:10.1074/jbc.M213054200

[5] Clifton IJ, Doan LX, Sleeman MC, Topf M, Suzuki H, Wilmouth RC, Schofield CJ. Crystal structure of carbapenem synthase (CarC). J Biol Chem. 2003 Jun 6;278(23):20843-50. Epub 2003 Feb 28. PMID:12611886 doi:10.1074/jbc.M213054200

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[2]

[3]

[4]

[5]

@@ Line 2: / Line 2: @@
 <StructureSection load='1nx4' size='340' side='right' caption='[[1nx4]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1nx4]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Pectobacterium_carotovorum Pectobacterium carotovorum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NX4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1NX4 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1nx4]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_carotovorus"_jones_1901 "bacillus carotovorus" jones 1901]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NX4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1NX4 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AKG:2-OXOGLUTARIC+ACID'>AKG</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1nx8|1nx8]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CarC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=554 Pectobacterium carotovorum])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CarC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=554 "Bacillus carotovorus" Jones 1901])</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=1nx4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nx4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1nx4 RCSB], [http://www.ebi.ac.uk/pdbsum/1nx4 PDBsum]</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=1nx4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nx4 OCA], [http://pdbe.org/1nx4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1nx4 RCSB], [http://www.ebi.ac.uk/pdbsum/1nx4 PDBsum]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/Q9XB59_ERWCA Q9XB59_ERWCA]] Catalyzes the Fe(2+) and alpha-ketoglutarate-dependent conversion of (3S,5S)-carbapenam to (5R)-carbapenem, an essential step in carbapenem antibiotic biosynthesis.<ref>PMID:9402024</ref> <ref>PMID:12848554</ref> <ref>PMID:15174175</ref> <ref>PMID:12611886</ref>
+[[http://www.uniprot.org/uniprot/CARC_PECCC CARC_PECCC]] Catalyzes the Fe(2+) and alpha-ketoglutarate-dependent conversion of (3S,5S)-carbapenam to (5R)-carbapenem, an essential step in carbapenem antibiotic biosynthesis.<ref>PMID:9402024</ref> <ref>PMID:12848554</ref> <ref>PMID:15174175</ref> <ref>PMID:12611886</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 29: / Line 29: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 1nx4" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Pectobacterium carotovorum]]
+[[Category: Bacillus carotovorus jones 1901]]
 [[Category: Clifton, I J]]
 [[Category: Doan, L X]]

1nx4: Difference between revisions

Revision as of 09:29, 11 September 2015

The crystal structure of carbapenem synthase (CarC)

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

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