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| | <StructureSection load='4x58' size='340' side='right'caption='[[4x58]], [[Resolution|resolution]] 1.75Å' scene=''> | | <StructureSection load='4x58' size='340' side='right'caption='[[4x58]], [[Resolution|resolution]] 1.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4x58]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4X58 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4X58 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4x58]] 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=4X58 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4X58 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MLT:D-MALATE'>MLT</scene>, <scene name='pdbligand=PRP:ALPHA-PHOSPHORIBOSYLPYROPHOSPHORIC+ACID'>PRP</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MLT:D-MALATE'>MLT</scene>, <scene name='pdbligand=PRP:ALPHA-PHOSPHORIBOSYLPYROPHOSPHORIC+ACID'>PRP</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4x59|4x59]], [[4x5a|4x5a]], [[4x5b|4x5b]], [[4x5c|4x5c]], [[4x5d|4x5d]], [[4x5e|4x5e]]</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=4x58 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x58 OCA], [https://pdbe.org/4x58 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4x58 RCSB], [https://www.ebi.ac.uk/pdbsum/4x58 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4x58 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">trpD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Anthranilate_phosphoribosyltransferase Anthranilate phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.18 2.4.2.18] </span></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=4x58 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x58 OCA], [http://pdbe.org/4x58 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4x58 RCSB], [http://www.ebi.ac.uk/pdbsum/4x58 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4x58 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TRPD_MYCTA TRPD_MYCTA]] Catalyzes the transfer of the phosphoribosyl group of 5-phosphorylribose-1-pyrophosphate (PRPP) to anthranilate to yield N-(5'-phosphoribosyl)-anthranilate (PRA). | + | [https://www.uniprot.org/uniprot/TRPD_MYCTU TRPD_MYCTU] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Phosphoribosyltransferase|Phosphoribosyltransferase]] | + | *[[Phosphoribosyltransferase 3D structures|Phosphoribosyltransferase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Anthranilate phosphoribosyltransferase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Cookson, T V.M]] | |
| - | [[Category: Evans, G L]] | |
| - | [[Category: Lott, J S]] | |
| - | [[Category: Parker, E J]] | |
| - | [[Category: Anthranilic acid]] | |
| - | [[Category: Magnesium]] | |
| - | [[Category: Magnesium binding]] | |
| - | [[Category: Mutation]] | |
| | [[Category: Mycobacterium tuberculosis]] | | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: Phosphoribosyl pyrophosphate]] | + | [[Category: Cookson TVM]] |
| - | [[Category: Transferase]] | + | [[Category: Evans GL]] |
| - | [[Category: Tryptophan]] | + | [[Category: Lott JS]] |
| | + | [[Category: Parker EJ]] |
| Structural highlights
Function
TRPD_MYCTU
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Cookson TV, Evans GL, Castell A, Baker EN, Lott JS, Parker EJ. Structures of Mycobacterium tuberculosis Anthranilate Phosphoribosyltransferase Variants Reveal the Conformational Changes That Facilitate Delivery of the Substrate to the Active Site. Biochemistry. 2015 Oct 6;54(39):6082-92. doi: 10.1021/acs.biochem.5b00612. PMID:26356348 doi:http://dx.doi.org/10.1021/acs.biochem.5b00612
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