View source for 7xgl


==Quinolinate Phosphoribosyl Transferase (QAPRTase) from Streptomyces pyridomyceticus NRRL B-2517 in Apo form==
<StructureSection load='7xgl' size='340' side='right'caption='[[7xgl]], [[Resolution|resolution]] 2.11&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7xgl]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_pyridomyceticus Streptomyces pyridomyceticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7XGL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XGL 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]] 2.11&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0L1:HEXANEDIOIC+ACID'>0L1</scene>, <scene name='pdbligand=144:TRIS-HYDROXYMETHYL-METHYL-AMMONIUM'>144</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=7xgl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xgl OCA], [https://pdbe.org/7xgl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xgl RCSB], [https://www.ebi.ac.uk/pdbsum/7xgl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xgl ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Pyridomycin is a potent antimycobacterial natural product by specifically inhibiting InhA, a clinically validated antituberculosis drug discovery target. Pyridyl moieties of pyridomycin play an essential role in inhibiting InhA by occupying the reduced form of the nicotinamide adenine dinucleotide (NADH) cofactor binding site. Herein, we biochemically characterize PyrZ that is a multifunctional NadC homologue and catalyzes the successive formation, dephosphorylation, and ribose hydrolysis of nicotinic acid mononucleotide (NAMN) to generate nicotinic acid (NA), a biosynthetic precursor for the pyridyl moiety of pyridomycin. Crystal structures of PyrZ in complex with substrate quinolinic acid (QA) and the final product NA revealed a specific salt bridge formed between K184 and the C3-carboxyl group of QA. This interaction positions QA for accepting the phosphoribosyl group to generate NAMN, retains NAMN within the active site, and mediates its translocation to nucleophile D296 for dephosphorylation. Combining kinetic and thermodynamic analysis with site-directed mutagenesis, the catalytic mechanism of PyrZ dephosphorylation was proposed. Our study discovered an alternative and concise NA biosynthetic pathway involving a unique multifunctional enzyme.

Bifunctional NadC Homologue PyrZ Catalyzes Nicotinic Acid Formation in Pyridomycin Biosynthesis.,Zhou Z, Yang X, Huang T, Zheng J, Deng Z, Dai S, Lin S ACS Chem Biol. 2023 Jan 20;18(1):141-150. doi: 10.1021/acschembio.2c00773. Epub , 2022 Dec 14. PMID:36517246<ref>PMID:36517246</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7xgl" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptomyces pyridomyceticus]]
[[Category: Dai S]]
[[Category: Deng Z]]
[[Category: Huang T]]
[[Category: Liang R]]
[[Category: Lin S]]
[[Category: Wang X]]
[[Category: Yang X]]
[[Category: Zheng J]]
[[Category: Zhou Z]]