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4yub

From Proteopedia

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Crystal structure of human Nicotinic Acid Phosphoribosyltransferase

Structural highlights

4yub is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.9Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PNCB_HUMAN Catalyzes the conversion of nicotinic acid (NA) to NA mononucleotide (NaMN). Essential for NA to increase cellular NAD levels and prevent oxidative stress of the cells.^[1] Catalyzes the synthesis of beta-nicotinate D-ribonucleotide from nicotinate and 5-phospho-D-ribose 1-phosphate at the expense of ATP.

Publication Abstract from PubMed

Nicotinic acid phosphoribosyltransferase (EC 2.4.2.11) (NaPRTase) is the rate-limiting enzyme in the three-step Preiss-Handler pathway for the biosynthesis of NAD. The enzyme catalyzes the conversion of nicotinic acid (Na) and 5-phosphoribosyl-1-pyrophosphate (PRPP) to nicotinic acid mononucleotide (NaMN) and pyrophosphate (PPi). Several studies have underlined the importance of NaPRTase for NAD homeostasis in mammals, but no crystallographic data are available for this enzyme from higher eukaryotes. Here, we report the crystal structure of human NaPRTase that was solved by molecular replacement at a resolution of 2.9 A in its ligand-free form. Our structural data allow the assignment of human NaPRTase to the type II phosphoribosyltransferase subfamily and reveal that the enzyme consists of two domains and functions as a dimer with the active site located at the interface of the monomers. The substrate-binding mode was analyzed by molecular docking simulation and provides hints into the catalytic mechanism. Moreover, structural comparison of human NaPRTase with the other two human type II phosphoribosyltransferases involved in NAD biosynthesis, quinolinate phosphoribosyltransferase and nicotinamide phosphoribosyltransferase, reveals that while the three enzymes share a conserved overall structure, a few distinctive structural traits can be identified. In particular, we show that NaPRTase lacks a tunnel that, in nicotinamide phosphoribosiltransferase, represents the binding site of its potent and selective inhibitor FK866, currently used in clinical trials as an antitumoral agent.

Crystal structure of human nicotinic acid phosphoribosyltransferase.,Marletta AS, Massarotti A, Orsomando G, Magni G, Rizzi M, Garavaglia S FEBS Open Bio. 2015 May 7;5:419-28. doi: 10.1016/j.fob.2015.05.002. eCollection, 2015. PMID:26042198^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Hara N, Yamada K, Shibata T, Osago H, Hashimoto T, Tsuchiya M. Elevation of cellular NAD levels by nicotinic acid and involvement of nicotinic acid phosphoribosyltransferase in human cells. J Biol Chem. 2007 Aug 24;282(34):24574-82. Epub 2007 Jun 29. PMID:17604275 doi:http://dx.doi.org/10.1074/jbc.M610357200
↑ Marletta AS, Massarotti A, Orsomando G, Magni G, Rizzi M, Garavaglia S. Crystal structure of human nicotinic acid phosphoribosyltransferase. FEBS Open Bio. 2015 May 7;5:419-28. doi: 10.1016/j.fob.2015.05.002. eCollection, 2015. PMID:26042198 doi:http://dx.doi.org/10.1016/j.fob.2015.05.002

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4yub"

Categories: Homo sapiens | Large Structures | Garavaglia S | Marletta AS | Rizzi M

@@ Line 1: / Line 1: @@
 ==Crystal structure of human Nicotinic Acid Phosphoribosyltransferase==
-<StructureSection load='4yub' size='340' side='right' caption='[[4yub]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
+<StructureSection load='4yub' size='340' side='right'caption='[[4yub]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4yub]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YUB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YUB FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4yub]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YUB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YUB FirstGlance]. <br>
-</td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Nicotinate_phosphoribosyltransferase Nicotinate phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.4.21 6.3.4.21] </span></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9&#8491;</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=4yub FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yub OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4yub RCSB], [http://www.ebi.ac.uk/pdbsum/4yub PDBsum]</span></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=4yub FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yub OCA], [https://pdbe.org/4yub PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yub RCSB], [https://www.ebi.ac.uk/pdbsum/4yub PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yub ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/PNCB_HUMAN PNCB_HUMAN]] Catalyzes the conversion of nicotinic acid (NA) to NA mononucleotide (NaMN). Essential for NA to increase cellular NAD levels and prevent oxidative stress of the cells.<ref>PMID:17604275</ref>   Catalyzes the synthesis of beta-nicotinate D-ribonucleotide from nicotinate and 5-phospho-D-ribose 1-phosphate at the expense of ATP.
+[https://www.uniprot.org/uniprot/PNCB_HUMAN PNCB_HUMAN] Catalyzes the conversion of nicotinic acid (NA) to NA mononucleotide (NaMN). Essential for NA to increase cellular NAD levels and prevent oxidative stress of the cells.<ref>PMID:17604275</ref>   Catalyzes the synthesis of beta-nicotinate D-ribonucleotide from nicotinate and 5-phospho-D-ribose 1-phosphate at the expense of ATP.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 16: / Line 17: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4yub" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Phosphoribosyltransferase 3D structures|Phosphoribosyltransferase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Nicotinate phosphoribosyltransferase]]
+[[Category: Homo sapiens]]
-[[Category: Garavaglia, S]]
+[[Category: Large Structures]]
-[[Category: Marletta, A S]]
+[[Category: Garavaglia S]]
-[[Category: Rizzi, M]]
+[[Category: Marletta AS]]
-[[Category: Fk866 recycling]]
+[[Category: Rizzi M]]
-[[Category: Ligase]]
-[[Category: Nad biosynthesis]]
-[[Category: Nad pathway]]
-[[Category: Nicotinic acid preiss handler pathway]]
-[[Category: Phosphoribosyl transferase]]

4yub

From Proteopedia

Current revision

Crystal structure of human Nicotinic Acid Phosphoribosyltransferase

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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