View source for 2i6u


==Crystal Structure of Ornithine Carbamoyltransferase complexed with Carbamoyl Phosphate and L-Norvaline from Mycobacterium tuberculosis (Rv1656) at 2.2 A==
<StructureSection load='2i6u' size='340' side='right'caption='[[2i6u]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2i6u]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I6U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2I6U 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]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CP:PHOSPHORIC+ACID+MONO(FORMAMIDE)ESTER'>CP</scene>, <scene name='pdbligand=NVA:NORVALINE'>NVA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=2i6u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i6u OCA], [https://pdbe.org/2i6u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2i6u RCSB], [https://www.ebi.ac.uk/pdbsum/2i6u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2i6u ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/OTC_MYCTU OTC_MYCTU] Reversibly catalyzes the transfer of the carbamoyl group from carbamoyl phosphate (CP) to the N(epsilon) atom of ornithine (ORN) to produce L-citrulline, which is a substrate for argininosuccinate synthetase, the enzyme involved in the final step in arginine biosynthesis (By similarity).[HAMAP-Rule:MF_01109]
== 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/i6/2i6u_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=2i6u ConSurf].
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== Publication Abstract from PubMed ==
Mycobacterium tuberculosis ornithine carbamoyltransferase (Mtb OTC) catalyzes the sixth step in arginine biosynthesis; it produces citrulline from carbamoyl phosphate (CP) and ornithine (ORN). Here, we report the crystal structures of Mtb OTC in orthorhombic (form I) and hexagonal (form II) space groups. The molecules in form II are complexed with CP and l-norvaline (NVA); the latter is a competitive inhibitor of OTC. The asymmetric unit in form I contains a pseudo hexamer with 32 point group symmetry. The CP and NVA in form II induce a remarkable conformational change in the 80s and the 240s loops with the displacement of these loops towards the active site. The displacement of these loops is strikingly different from that seen in other OTC structures. In addition, the ligands induce a domain closure of 4.4 degrees in form II. Sequence comparison of active-site residues of Mtb OTC with several other OTCs of known structure reveals that they are virtually identical. The interactions involving the active-site residues of Mtb OTC with CP and NVA and a modeling study of ORN in the form II structure strongly rule out an earlier proposed mechanistic role of Cys264 in catalysis and suggest a possible mechanism for OTC. Our results strongly support the view that ORN with an already deprotonated N(epsilon) atom is the species that binds to the enzyme and that one of the phosphate oxygen atoms of CP is likely to be involved in accepting a proton from the doubly protonated N(epsilon) atom of ORN. We have interpreted this deprotonation as part of the collapse of the transition state of the reaction.

The crystal structures of ornithine carbamoyltransferase from Mycobacterium tuberculosis and its ternary complex with carbamoyl phosphate and L-norvaline reveal the enzyme's catalytic mechanism.,Sankaranarayanan R, Cherney MM, Cherney LT, Garen CR, Moradian F, James MN J Mol Biol. 2008 Jan 25;375(4):1052-63. Epub 2007 Nov 19. PMID:18062991<ref>PMID:18062991</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2i6u" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ornithine carbamoyltransferase|Ornithine carbamoyltransferase]]
*[[Ornithine carbamoyltransferase 3D structures|Ornithine carbamoyltransferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Cherney LT]]
[[Category: Cherney MM]]
[[Category: Garen C]]
[[Category: James MNG]]
[[Category: Moradian F]]
[[Category: Sankaranarayanan R]]