4x5c: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
''' | ==Anthranilate phosphoribosyltransferase variant R193L from Mycobacterium tuberculosis with pyrophosphate/PRPP and Mg2+ bound== | ||
<StructureSection load='4x5c' size='340' side='right' caption='[[4x5c]], [[Resolution|resolution]] 2.33Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4x5c]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4X5C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4X5C FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=POP:PYROPHOSPHATE+2-'>POP</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">[[4x58|4x58]], [[4x59|4x59]], [[4x5a|4x5a]], [[4x5b|4x5b]], [[4x5d|4x5d]], [[4x5e|4x5e]]</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=4x5c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x5c OCA], [http://pdbe.org/4x5c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4x5c RCSB], [http://www.ebi.ac.uk/pdbsum/4x5c PDBsum]</span></td></tr> | |||
</table> | |||
== 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). | |||
<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> | |||
</div> | |||
<div class="pdbe-citations 4x5c" style="background-color:#fffaf0;"></div> | |||
[[Category: | == References == | ||
[[Category: Lott, J | <references/> | ||
[[Category: Parker, E | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: Anthranilate phosphoribosyltransferase]] | |||
[[Category: Cookson, T V.M]] | |||
[[Category: Lott, J S]] | |||
[[Category: Parker, E J]] | |||
[[Category: Anthranilic acid]] | |||
[[Category: Magnesium]] | |||
[[Category: Magnesium binding]] | |||
[[Category: Mutation]] | |||
[[Category: Mycobacterium tuberculosis]] | |||
[[Category: Phosphoribosyl pyrophosphate]] | |||
[[Category: Transferase]] | |||
[[Category: Tryptophan]] | |||
Revision as of 07:37, 1 December 2015
Anthranilate phosphoribosyltransferase variant R193L from Mycobacterium tuberculosis with pyrophosphate/PRPP and Mg2+ boundAnthranilate phosphoribosyltransferase variant R193L from Mycobacterium tuberculosis with pyrophosphate/PRPP and Mg2+ bound
Structural highlights
Function[TRPD_MYCTA] Catalyzes the transfer of the phosphoribosyl group of 5-phosphorylribose-1-pyrophosphate (PRPP) to anthranilate to yield N-(5'-phosphoribosyl)-anthranilate (PRA). Publication Abstract from PubMedAnthranilate 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. References
|
| ||||||||||||||||||||