1nut

From Proteopedia

(Difference between revisions)

Current revision

CRYSTAL STRUCTURE OF HUMAN CYTOSOLIC NMN/NaMN ADENYLYLTRANSFERASE COMPLEXED WITH ATP ANALOG

Structural highlights

1nut 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 1.9Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NMNA3_HUMAN Catalyzes the formation of NAD(+) from nicotinamide mononucleotide (NMN) and ATP. Can also use the deamidated form; nicotinic acid mononucleotide (NaMN) as substrate with the same efficiency. Can use triazofurin monophosphate (TrMP) as substrate. Can also use GTP and ITP as nucleotide donors. Also catalyzes the reverse reaction, i.e. the pyrophosphorolytic cleavage of NAD(+). For the pyrophosphorolytic activity, can use NAD (+), NADH, NAAD, nicotinic acid adenine dinucleotide phosphate (NHD), nicotinamide guanine dinucleotide (NGD) as substrates. Fails to cleave phosphorylated dinucleotides NADP(+), NADPH and NAADP(+). Protects against axonal degeneration following injury.^[1] ^[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Pyridine dinucleotides (NAD and NADP) are ubiquitous cofactors involved in hundreds of redox reactions essential for the energy transduction and metabolism in all living cells. In addition, NAD also serves as a substrate for ADP-ribosylation of a number of nuclear proteins, for silent information regulator 2 (Sir2)-like histone deacetylase that is involved in gene silencing regulation, and for cyclic ADP ribose (cADPR)-dependent Ca(2+) signaling. Pyridine nucleotide adenylyltransferase (PNAT) is an indispensable central enzyme in the NAD biosynthesis pathways catalyzing the condensation of pyridine mononucleotide (NMN or NaMN) with the AMP moiety of ATP to form NAD (or NaAD). Here we report the identification and structural characterization of a novel human PNAT (hsPNAT-3) that is located in the cytoplasm and mitochondria. Its subcellular localization and tissue distribution are distinct from the previously identified human nuclear PNAT-1 and PNAT-2. Detailed structural analysis of PNAT-3 in its apo form and in complex with its substrate(s) or product revealed the catalytic mechanism of the enzyme. The characterization of the cytosolic human PNAT-3 provided compelling evidence that the final steps of NAD biosynthesis pathways may exist in mammalian cytoplasm and mitochondria, potentially contributing to their NAD/NADP pool.

Structural characterization of a human cytosolic NMN/NaMN adenylyltransferase and implication in human NAD biosynthesis.,Zhang X, Kurnasov OV, Karthikeyan S, Grishin NV, Osterman AL, Zhang H J Biol Chem. 2003 Apr 11;278(15):13503-11. Epub 2003 Feb 6. PMID:12574164^[3]

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

References

↑ Berger F, Lau C, Dahlmann M, Ziegler M. Subcellular compartmentation and differential catalytic properties of the three human nicotinamide mononucleotide adenylyltransferase isoforms. J Biol Chem. 2005 Oct 28;280(43):36334-41. Epub 2005 Aug 23. PMID:16118205 doi:http://dx.doi.org/10.1074/jbc.M508660200
↑ Sorci L, Cimadamore F, Scotti S, Petrelli R, Cappellacci L, Franchetti P, Orsomando G, Magni G. Initial-rate kinetics of human NMN-adenylyltransferases: substrate and metal ion specificity, inhibition by products and multisubstrate analogues, and isozyme contributions to NAD+ biosynthesis. Biochemistry. 2007 Apr 24;46(16):4912-22. Epub 2007 Apr 3. PMID:17402747 doi:10.1021/bi6023379
↑ Zhang X, Kurnasov OV, Karthikeyan S, Grishin NV, Osterman AL, Zhang H. Structural characterization of a human cytosolic NMN/NaMN adenylyltransferase and implication in human NAD biosynthesis. J Biol Chem. 2003 Apr 11;278(15):13503-11. Epub 2003 Feb 6. PMID:12574164 doi:10.1074/jbc.M300073200

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1nut"

@@ Line 1: / Line 1: @@
-[[Image:1nut.png|left|200px]]
-<!--
+==CRYSTAL STRUCTURE OF HUMAN CYTOSOLIC NMN/NaMN ADENYLYLTRANSFERASE COMPLEXED WITH ATP ANALOG==
-The line below this paragraph, containing "STRUCTURE_1nut", creates the "Structure Box" on the page.
+<StructureSection load='1nut' size='340' side='right'caption='[[1nut]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[1nut]] 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=1NUT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NUT FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=APC:DIPHOSPHOMETHYLPHOSPHONIC+ACID+ADENOSYL+ESTER'>APC</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-{{STRUCTURE_1nut|  PDB=1nut  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1nut FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nut OCA], [https://pdbe.org/1nut PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nut RCSB], [https://www.ebi.ac.uk/pdbsum/1nut PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nut ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/NMNA3_HUMAN NMNA3_HUMAN] Catalyzes the formation of NAD(+) from nicotinamide mononucleotide (NMN) and ATP. Can also use the deamidated form; nicotinic acid mononucleotide (NaMN) as substrate with the same efficiency. Can use triazofurin monophosphate (TrMP) as substrate. Can also use GTP and ITP as nucleotide donors. Also catalyzes the reverse reaction, i.e. the pyrophosphorolytic cleavage of NAD(+). For the pyrophosphorolytic activity, can use NAD (+), NADH, NAAD, nicotinic acid adenine dinucleotide phosphate (NHD), nicotinamide guanine dinucleotide (NGD) as substrates. Fails to cleave phosphorylated dinucleotides NADP(+), NADPH and NAADP(+). Protects against axonal degeneration following injury.<ref>PMID:16118205</ref> <ref>PMID:17402747</ref>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nu/1nut_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1nut ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Pyridine dinucleotides (NAD and NADP) are ubiquitous cofactors involved in hundreds of redox reactions essential for the energy transduction and metabolism in all living cells. In addition, NAD also serves as a substrate for ADP-ribosylation of a number of nuclear proteins, for silent information regulator 2 (Sir2)-like histone deacetylase that is involved in gene silencing regulation, and for cyclic ADP ribose (cADPR)-dependent Ca(2+) signaling. Pyridine nucleotide adenylyltransferase (PNAT) is an indispensable central enzyme in the NAD biosynthesis pathways catalyzing the condensation of pyridine mononucleotide (NMN or NaMN) with the AMP moiety of ATP to form NAD (or NaAD). Here we report the identification and structural characterization of a novel human PNAT (hsPNAT-3) that is located in the cytoplasm and mitochondria. Its subcellular localization and tissue distribution are distinct from the previously identified human nuclear PNAT-1 and PNAT-2. Detailed structural analysis of PNAT-3 in its apo form and in complex with its substrate(s) or product revealed the catalytic mechanism of the enzyme. The characterization of the cytosolic human PNAT-3 provided compelling evidence that the final steps of NAD biosynthesis pathways may exist in mammalian cytoplasm and mitochondria, potentially contributing to their NAD/NADP pool.
-===CRYSTAL STRUCTURE OF HUMAN CYTOSOLIC NMN/NaMN ADENYLYLTRANSFERASE COMPLEXED WITH ATP ANALOG===
+Structural characterization of a human cytosolic NMN/NaMN adenylyltransferase and implication in human NAD biosynthesis.,Zhang X, Kurnasov OV, Karthikeyan S, Grishin NV, Osterman AL, Zhang H J Biol Chem. 2003 Apr 11;278(15):13503-11. Epub 2003 Feb 6. PMID:12574164<ref>PMID:12574164</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-<!--
+</div>
-The line below this paragraph, {{ABSTRACT_PUBMED_12574164}}, adds the Publication Abstract to the page
+<div class="pdbe-citations 1nut" style="background-color:#fffaf0;"></div>
-(as it appears on PubMed at http://www.pubmed.gov), where 12574164 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_12574164}}
+__TOC__
+</StructureSection>
-==About this Structure==
-[[1nut]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NUT OCA].
-==Reference==
-<ref group="xtra">PMID:012574164</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
-[[Category: Grishin, N V.]]
+[[Category: Large Structures]]
-[[Category: Karthikeyan, S.]]
+[[Category: Grishin NV]]
-[[Category: Kurnasov, O V.]]
+[[Category: Karthikeyan S]]
-[[Category: Osterman, A L.]]
+[[Category: Kurnasov OV]]
-[[Category: Zhang, H.]]
+[[Category: Osterman AL]]
-[[Category: Zhang, X.]]
+[[Category: Zhang H]]
-[[Category: Enzyme catalysis]]
+[[Category: Zhang X]]
-[[Category: Mitochondria]]
-[[Category: Nad biosynthesis]]
-[[Category: Pyridine adenylyltransferase]]
-[[Category: Transferase]]

1nut

From Proteopedia

Current revision

CRYSTAL STRUCTURE OF HUMAN CYTOSOLIC NMN/NaMN ADENYLYLTRANSFERASE COMPLEXED WITH ATP ANALOG

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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