2a7k: Difference between revisions

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[[Image:2a7k.gif|left|200px]]


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==carboxymethylproline synthase (CarB) from pectobacterium carotovora, apo enzyme==
The line below this paragraph, containing "STRUCTURE_2a7k", creates the "Structure Box" on the page.
<StructureSection load='2a7k' size='340' side='right'caption='[[2a7k]], [[Resolution|resolution]] 2.24&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<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>
or leave the SCENE parameter empty for the default display.
</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'>[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>
{{STRUCTURE_2a7k|  PDB=2a7k  |  SCENE= }}
</table>
 
== Function ==
'''carboxymethylproline synthase (CarB) from pectobacterium carotovora, apo enzyme'''
[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 ==
 
[[Image:Consurf_key_small.gif|200px|right]]
==Overview==
Check<jmol>
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.
  <jmolCheckbox>
 
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a7/2a7k_consurf.spt"</scriptWhenChecked>
==About this Structure==
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
2A7K is a [[Single protein]] structure of 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=2A7K OCA].  
    <text>to colour the structure by Evolutionary Conservation</text>
 
  </jmolCheckbox>
==Reference==
</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].
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:[http://www.ncbi.nlm.nih.gov/pubmed/16096274 16096274]
<div style="clear:both"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Pectobacterium carotovorum]]
[[Category: Pectobacterium carotovorum]]
[[Category: Single protein]]
[[Category: Batchelar ET]]
[[Category: Batchelar, E T.]]
[[Category: McDonough MA]]
[[Category: McDonough, M A.]]
[[Category: Schofield CJ]]
[[Category: Schofield, C J.]]
[[Category: Sleeman MC]]
[[Category: Sleeman, M C.]]
[[Category: Sorensen JL]]
[[Category: Sorensen, J L.]]
[[Category: Antibiotic]]
[[Category: Beta-lactam]]
[[Category: Carbapenam]]
[[Category: Carbapenem]]
[[Category: Crotonase]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 18:42:31 2008''

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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