4x5e: Difference between revisions
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==Anthranilate phosphoribosyltransferase variant R194A from Mycobacterium tuberculosis with pyrophosphate, Mg2+ and anthranilate bound== | |||
<StructureSection load='4x5e' size='340' side='right'caption='[[4x5e]], [[Resolution|resolution]] 1.77Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4x5e]] is a 2 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=4X5E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4X5E 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]] 1.77Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BE2:2-AMINOBENZOIC+ACID'>BE2</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=POP:PYROPHOSPHATE+2-'>POP</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=4x5e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x5e OCA], [https://pdbe.org/4x5e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4x5e RCSB], [https://www.ebi.ac.uk/pdbsum/4x5e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4x5e ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/TRPD_MYCTU TRPD_MYCTU] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Anthranilate phosphoribosyltransferase (AnPRT) is essential for the biosynthesis of tryptophan in Mycobacterium tuberculosis (Mtb). This enzyme catalyzes the second committed step in tryptophan biosynthesis, the Mg(2+)-dependent reaction between 5'-phosphoribosyl-1'-pyrophosphate (PRPP) and anthranilate. The roles of residues predicted to be involved in anthranilate binding have been tested by the analysis of six Mtb-AnPRT variant proteins. Kinetic analysis showed that five of six variants were active and identified the conserved residue R193 as being crucial for both anthranilate binding and catalytic function. Crystal structures of these Mtb-AnPRT variants reveal the ability of anthranilate to bind in three sites along an extended anthranilate tunnel and expose the role of the mobile beta2-alpha6 loop in facilitating the enzyme's sequential reaction mechanism. The beta2-alpha6 loop moves sequentially between a "folded" conformation, partially occluding the anthranilate tunnel, via an "open" position to a "closed" conformation, which supports PRPP binding and allows anthranilate access via the tunnel to the active site. The return of the beta2-alpha6 loop to the "folded" conformation completes the catalytic cycle, concordantly allowing the active site to eject the product PRA and rebind anthranilate at the opening of the anthranilate tunnel for subsequent reactions. Multiple anthranilate molecules blocking the anthranilate tunnel prevent the beta2-alpha6 loop from undergoing the conformational changes required for catalysis, thus accounting for the unusual substrate inhibition of this enzyme. | |||
Structures of Mycobacterium tuberculosis Anthranilate Phosphoribosyltransferase Variants Reveal the Conformational Changes That Facilitate Delivery of the Substrate to the Active Site.,Cookson TV, Evans GL, Castell A, Baker EN, Lott JS, Parker EJ Biochemistry. 2015 Oct 6;54(39):6082-92. doi: 10.1021/acs.biochem.5b00612. PMID:26356348<ref>PMID:26356348</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 4x5e" style="background-color:#fffaf0;"></div> | ||
[[Category: Evans | |||
[[Category: | ==See Also== | ||
[[Category: | *[[Phosphoribosyltransferase 3D structures|Phosphoribosyltransferase 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mycobacterium tuberculosis]] | |||
[[Category: Cookson TVM]] | |||
[[Category: Evans GL]] | |||
[[Category: Lott JS]] | |||
[[Category: Parker EJ]] | |||