View source for 5lhu


==ATP Phosphoribosyltransferase from Mycobacterium tuberculosis in complex with the allosteric inhibitor L-Histidine==
<StructureSection load='5lhu' size='340' side='right'caption='[[5lhu]], [[Resolution|resolution]] 2.02&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5lhu]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LHU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LHU 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]] 2.02&#8491;</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=HIS:HISTIDINE'>HIS</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=5lhu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lhu OCA], [https://pdbe.org/5lhu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lhu RCSB], [https://www.ebi.ac.uk/pdbsum/5lhu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lhu ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HIS1_MYCTU HIS1_MYCTU] Catalyzes the condensation of ATP and 5-phosphoribose 1-diphosphate to form N'-(5'-phosphoribosyl)-ATP (PR-ATP). Has a crucial role in the pathway because the rate of histidine biosynthesis seems to be controlled primarily by regulation of HisG enzymatic activity (By similarity).
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== Publication Abstract from PubMed ==
ATP-phosphoribosyltransferase (ATP-PRT) is a hexameric enzyme in conformational equilibrium between an open and seemingly active state and a closed and presumably inhibited form. The structure-function relationship of allosteric regulation in this system is still not fully understood. Here, we develop a screening strategy for modulators of ATP-PRT and identify 3-(2-thienyl)-L-alanine (TIH) as an allosteric activator of this enzyme. Kinetic analysis reveals co-occupancy of the allosteric sites by TIH and L-histidine. Crystallographic and native ion-mobility mass spectrometry data show that the TIH-bound activated form of the enzyme closely resembles the inhibited L-histidine-bound closed conformation, revealing the uncoupling between ATP-PRT open and closed conformations and its functional state. These findings suggest that dynamic processes are responsible for ATP-PRT allosteric regulation and that similar mechanisms might also be found in other enzymes bearing a ferredoxin-like allosteric domain.Active and inactive state ATP-phosphoribosyltransferases (ATP-PRTs) are believed to have different conformations. Here the authors show that in both states, ATP-PRT has a similar structural arrangement, suggesting that dynamic alterations are involved in ATP-PRT regulation by allosteric modulators.

Uncoupling conformational states from activity in an allosteric enzyme.,Pisco JP, Chiara C, Pacholarz KJ, Garza-Garcia A, Ogrodowicz RW, Walker PA, Barran PE, Smerdon SJ, Carvalho LPS Nat Commun. 2017 Aug 7;8(1):203. doi: 10.1038/s41467-017-00224-0. PMID:28781362<ref>PMID:28781362</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 5lhu" style="background-color:#fffaf0;"></div>

==See Also==
*[[ATP phosphoribosyl transferase 3D structures|ATP phosphoribosyl transferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis H37Rv]]
[[Category: Ogrodowicz R]]
[[Category: Pisco JP]]
[[Category: Smerdon SJ]]
[[Category: Walker PA]]
[[Category: De Carvalho LP]]
[[Category: De Chiara C]]