1upb: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| (19 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
== | ==Carboxyethylarginine synthase from Streptomyces clavuligerus== | ||
The initial step in the biosynthesis of the clinically important | <StructureSection load='1upb' size='340' side='right'caption='[[1upb]], [[Resolution|resolution]] 2.35Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1upb]] is a 4 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=1UPB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UPB FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.35Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TPP:THIAMINE+DIPHOSPHATE'>TPP</scene></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=1upb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1upb OCA], [https://pdbe.org/1upb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1upb RCSB], [https://www.ebi.ac.uk/pdbsum/1upb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1upb ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CEAS_STRCL CEAS_STRCL] Involved in the biosynthesis of the beta-lactamase inhibitor, clavulanic acid. Catalyzes the thiamine diphosphate (ThDP) dependent condensation of D-glyceraldehyde-3-phosphate (D-G3P) with L-arginine to yield the beta-amino acid, N2-(2-carboxyethyl)arginine (CEA) via a beta-elimination resulting in the formation of an enol which undergoes a second elimination to generate the alpha,beta-unsaturated acryloyl-ThDP.<ref>PMID:18052280</ref> <ref>PMID:19477162</ref> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/up/1upb_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</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=1upb ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The initial step in the biosynthesis of the clinically important beta-lactamase inhibitor clavulanic acid involves condensation of two primary metabolites, D-glyceraldehyde 3-phosphate and L-arginine, to give N2-(2-carboxyethyl)arginine, a beta-amino acid. This unusual N-C bond forming reaction is catalyzed by the thiamin diphosphate (ThP2)-dependent enzyme N2-(2-carboxyethyl)arginine synthase. Here we report the crystal structure of N2-(2-carboxyethyl)arginine synthase, complexed with ThP2 and Mg2+, to 2.35-A resolution. The structure was solved in two space groups, P2(1)2(1)2(1) and P2(1)2(1)2. In both, the enzyme is observed in a tetrameric form, composed of a dimer of two more tightly associated dimers, consistent with both mass spectrometric and gel filtration chromatography studies. Both ThP2 and Mg2+ cofactors are present at the active site, with ThP2 in a "V" conformation as in related enzymes. A sulfate anion is observed in the active site of the enzyme in a location proposed as a binding site for the phosphate group of the d-glyceraldehyde 3-phosphate substrate. The mechanistic implications of the active site arrangement are discussed, including the potential role of the aminopyrimidine ring of the ThP2. The structure will form a basis for future mechanistic and structural studies, as well as engineering aimed at production of alternative beta-amino acids. | |||
Crystal structure and mechanistic implications of N2-(2-carboxyethyl)arginine synthase, the first enzyme in the clavulanic acid biosynthesis pathway.,Caines ME, Elkins JM, Hewitson KS, Schofield CJ J Biol Chem. 2004 Feb 13;279(7):5685-92. Epub 2003 Nov 17. PMID:14623876<ref>PMID:14623876</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
[[Category: | <div class="pdbe-citations 1upb" style="background-color:#fffaf0;"></div> | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Streptomyces clavuligerus]] | [[Category: Streptomyces clavuligerus]] | ||
[[Category: Caines | [[Category: Caines MEC]] | ||
[[Category: Elkins | [[Category: Elkins JM]] | ||
[[Category: Hewitson | [[Category: Hewitson KS]] | ||
[[Category: Schofield | [[Category: Schofield CJ]] | ||
