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==carboxymethylproline synthase (CarB) from pectobacterium carotovora, apo enzyme==
==carboxymethylproline synthase (CarB) from pectobacterium carotovora, apo enzyme==
<StructureSection load='2a7k' size='340' side='right' caption='[[2a7k]], [[Resolution|resolution]] 2.24&Aring;' scene=''>
<StructureSection load='2a7k' size='340' side='right'caption='[[2a7k]], [[Resolution|resolution]] 2.24&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2a7k]] is a 9 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=2A7K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2A7K FirstGlance]. <br>
<table><tr><td colspan='2'>[[2a7k]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Pectobacterium_carotovorum Pectobacterium carotovorum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A7K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2A7K FirstGlance]. <br>
</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CarB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=554 "Bacillus carotovorus" Jones 1901])</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]] 2.24&#8491;</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=2a7k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a7k OCA], [http://pdbe.org/2a7k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2a7k RCSB], [http://www.ebi.ac.uk/pdbsum/2a7k PDBsum]</span></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=2a7k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a7k OCA], [https://pdbe.org/2a7k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2a7k RCSB], [https://www.ebi.ac.uk/pdbsum/2a7k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2a7k ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/Q9XB60_PECCA Q9XB60_PECCA]] Catalyzes the formation of (2S,5S)-carboxymethylproline (t-CMP) from malonyl-CoA and (S)-1-pyrroline-5-carboxylate, the first step in the biosynthesis of (5R)-carbapen-2-em-3-carboxylate, a beta-lactam antibiotic of the carbapenem class (PubMed:15595850, PubMed:14625287). Also catalyzes the independent decarboxylation of malonyl-CoA and methylmalonyl-CoA and the hydrolysis of CoA esters such as acetyl-CoA and propionyl-CoA (PubMed:15595850). Catalyzes the reaction with a C2 epimeric mixture of methylmalonyl-CoA to give a 55:45 mixture of (6R)- and (6S)-epimers of 6-methyl-t-CMP, under standard incubation conditions (PubMed:21505494).<ref>PMID:14625287</ref> <ref>PMID:15595850</ref> <ref>PMID:15726176</ref> <ref>PMID:18972478</ref> <ref>PMID:21505494</ref>
[https://www.uniprot.org/uniprot/CARB_PECCC CARB_PECCC] Catalyzes the formation of (2S,5S)-carboxymethylproline (t-CMP) from malonyl-CoA and (S)-1-pyrroline-5-carboxylate, the first step in the biosynthesis of (5R)-carbapen-2-em-3-carboxylate, a beta-lactam antibiotic of the carbapenem class (PubMed:15595850, PubMed:14625287). Also catalyzes the independent decarboxylation of malonyl-CoA and methylmalonyl-CoA and the hydrolysis of CoA esters such as acetyl-CoA and propionyl-CoA (PubMed:15595850). Catalyzes the reaction with a C2 epimeric mixture of methylmalonyl-CoA to give a 55:45 mixture of (6R)- and (6S)-epimers of 6-methyl-t-CMP, under standard incubation conditions (PubMed:21505494).<ref>PMID:14625287</ref> <ref>PMID:15595850</ref> <ref>PMID:15726176</ref> <ref>PMID:18972478</ref> <ref>PMID:21505494</ref>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a7/2a7k_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a7/2a7k_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
Line 18: Line 19:
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2a7k ConSurf].
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2a7k ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The first step in the biosynthesis of the medicinally important carbapenem family of beta-lactam antibiotics is catalyzed by carboxymethylproline synthase (CarB), a unique member of the crotonase superfamily. CarB catalyzes formation of (2S,5S)-carboxymethylproline [(2S,5S)-t-CMP] from malonyl-CoA and l-glutamate semialdehyde. In addition to using a cosubstrate, CarB catalyzes C-C and C-N bond formation processes as well as an acyl-coenzyme A hydrolysis reaction. We describe the crystal structure of CarB in the presence and absence of acetyl-CoA at 2.24 A and 3.15 A resolution, respectively. The structures reveal that CarB contains a conserved oxy-anion hole probably required for decarboxylation of malonyl-CoA and stabilization of the resultant enolate. Comparison of the structures reveals that conformational changes (involving His(229)) in the cavity predicted to bind l-glutamate semialdehyde occur on (co)substrate binding. Mechanisms for the formation of the carboxymethylproline ring are discussed in the light of the structures and the accompanying studies using isotopically labeled substrates; cyclization via 1,4-addition is consistent with the observed labeling results (providing that hydrogen exchange at the C-6 position of carboxymethylproline does not occur). The side chain of Glu(131) appears to be positioned to be involved in hydrolysis of the carboxymethylproline-CoA ester intermediate. Labeling experiments ruled out the possibility that hydrolysis proceeds via an anhydride in which water attacks a carbonyl derived from Glu(131), as proposed for 3-hydroxyisobutyryl-CoA hydrolase. The structural work will aid in mutagenesis studies directed at altering the selectivity of CarB to provide intermediates for the production of clinically useful carbapenems.
Structural and mechanistic studies on carboxymethylproline synthase (CarB), a unique member of the crotonase superfamily catalyzing the first step in carbapenem biosynthesis.,Sleeman MC, Sorensen JL, Batchelar ET, McDonough MA, Schofield CJ J Biol Chem. 2005 Oct 14;280(41):34956-65. Epub 2005 Aug 11. PMID:16096274<ref>PMID:16096274</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2a7k" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Bacillus carotovorus jones 1901]]
[[Category: Large Structures]]
[[Category: Batchelar, E T]]
[[Category: Pectobacterium carotovorum]]
[[Category: McDonough, M A]]
[[Category: Batchelar ET]]
[[Category: Schofield, C J]]
[[Category: McDonough MA]]
[[Category: Sleeman, M C]]
[[Category: Schofield CJ]]
[[Category: Sorensen, J L]]
[[Category: Sleeman MC]]
[[Category: Antibiotic]]
[[Category: Sorensen JL]]
[[Category: Beta-lactam]]
[[Category: Biosynthetic protein]]
[[Category: Carbapenam]]
[[Category: Carbapenem]]
[[Category: Crotonase]]

Latest revision as of 09:11, 14 February 2024

carboxymethylproline synthase (CarB) from pectobacterium carotovora, apo enzyme

2a7k, resolution 2.24Å

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