1gzu: Difference between revisions

Latest revision as of 11:26, 27 March 2024

Crystal Structure of Human Nicotinamide Mononucleotide Adenylyltransferase in Complex with NMN

Structural highlights

1gzu is a 3 chain structure with sequence from Homo sapiens. This structure supersedes the now removed PDB entry 1gry. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.9Å
Ligands:	MSE, NMN
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

NMNA1_HUMAN Defects in NMNAT1 are the cause of Leber congenital amaurosis 9 (LCA9) [MIM:608553. A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus.^[1] ^[2] ^[3] ^[4]

Function

NMNA1_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. Also catalyzes the reverse reaction, i.e. the pyrophosphorolytic cleavage of NAD(+). For the pyrophosphorolytic activity, prefers NAD(+) and NAAD as substrates and degrades NADH, nicotinic acid adenine dinucleotide phosphate (NHD) and nicotinamide guanine dinucleotide (NGD) less effectively. Fails to cleave phosphorylated dinucleotides NADP(+), NADPH and NAADP(+). Protects against axonal degeneration following mechanical or toxic insults.^[5]

Evolutionary Conservation

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

References

↑ Koenekoop RK, Wang H, Majewski J, Wang X, Lopez I, Ren H, Chen Y, Li Y, Fishman GA, Genead M, Schwartzentruber J, Solanki N, Traboulsi EI, Cheng J, Logan CV, McKibbin M, Hayward BE, Parry DA, Johnson CA, Nageeb M, Poulter JA, Mohamed MD, Jafri H, Rashid Y, Taylor GR, Keser V, Mardon G, Xu H, Inglehearn CF, Fu Q, Toomes C, Chen R. Mutations in NMNAT1 cause Leber congenital amaurosis and identify a new disease pathway for retinal degeneration. Nat Genet. 2012 Sep;44(9):1035-9. doi: 10.1038/ng.2356. Epub 2012 Jul 29. PMID:22842230 doi:10.1038/ng.2356
↑ Chiang PW, Wang J, Chen Y, Fu Q, Zhong J, Chen Y, Yi X, Wu R, Gan H, Shi Y, Chen Y, Barnett C, Wheaton D, Day M, Sutherland J, Heon E, Weleber RG, Gabriel LA, Cong P, Chuang K, Ye S, Sallum JM, Qi M. Exome sequencing identifies NMNAT1 mutations as a cause of Leber congenital amaurosis. Nat Genet. 2012 Sep;44(9):972-4. doi: 10.1038/ng.2370. Epub 2012 Jul 29. PMID:22842231 doi:10.1038/ng.2370
↑ Perrault I, Hanein S, Zanlonghi X, Serre V, Nicouleau M, Defoort-Delhemmes S, Delphin N, Fares-Taie L, Gerber S, Xerri O, Edelson C, Goldenberg A, Duncombe A, Le Meur G, Hamel C, Silva E, Nitschke P, Calvas P, Munnich A, Roche O, Dollfus H, Kaplan J, Rozet JM. Mutations in NMNAT1 cause Leber congenital amaurosis with early-onset severe macular and optic atrophy. Nat Genet. 2012 Sep;44(9):975-7. doi: 10.1038/ng.2357. Epub 2012 Jul 29. PMID:22842229 doi:10.1038/ng.2357
↑ Falk MJ, Zhang Q, Nakamaru-Ogiso E, Kannabiran C, Fonseca-Kelly Z, Chakarova C, Audo I, Mackay DS, Zeitz C, Borman AD, Staniszewska M, Shukla R, Palavalli L, Mohand-Said S, Waseem NH, Jalali S, Perin JC, Place E, Ostrovsky J, Xiao R, Bhattacharya SS, Consugar M, Webster AR, Sahel JA, Moore AT, Berson EL, Liu Q, Gai X, Pierce EA. NMNAT1 mutations cause Leber congenital amaurosis. Nat Genet. 2012 Sep;44(9):1040-5. doi: 10.1038/ng.2361. Epub 2012 Jul 29. PMID:22842227 doi:10.1038/ng.2361
↑ 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

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Koenekoop RK, Wang H, Majewski J, Wang X, Lopez I, Ren H, Chen Y, Li Y, Fishman GA, Genead M, Schwartzentruber J, Solanki N, Traboulsi EI, Cheng J, Logan CV, McKibbin M, Hayward BE, Parry DA, Johnson CA, Nageeb M, Poulter JA, Mohamed MD, Jafri H, Rashid Y, Taylor GR, Keser V, Mardon G, Xu H, Inglehearn CF, Fu Q, Toomes C, Chen R. Mutations in NMNAT1 cause Leber congenital amaurosis and identify a new disease pathway for retinal degeneration. Nat Genet. 2012 Sep;44(9):1035-9. doi: 10.1038/ng.2356. Epub 2012 Jul 29. PMID:22842230 doi:10.1038/ng.2356

[2] Chiang PW, Wang J, Chen Y, Fu Q, Zhong J, Chen Y, Yi X, Wu R, Gan H, Shi Y, Chen Y, Barnett C, Wheaton D, Day M, Sutherland J, Heon E, Weleber RG, Gabriel LA, Cong P, Chuang K, Ye S, Sallum JM, Qi M. Exome sequencing identifies NMNAT1 mutations as a cause of Leber congenital amaurosis. Nat Genet. 2012 Sep;44(9):972-4. doi: 10.1038/ng.2370. Epub 2012 Jul 29. PMID:22842231 doi:10.1038/ng.2370

[3] Perrault I, Hanein S, Zanlonghi X, Serre V, Nicouleau M, Defoort-Delhemmes S, Delphin N, Fares-Taie L, Gerber S, Xerri O, Edelson C, Goldenberg A, Duncombe A, Le Meur G, Hamel C, Silva E, Nitschke P, Calvas P, Munnich A, Roche O, Dollfus H, Kaplan J, Rozet JM. Mutations in NMNAT1 cause Leber congenital amaurosis with early-onset severe macular and optic atrophy. Nat Genet. 2012 Sep;44(9):975-7. doi: 10.1038/ng.2357. Epub 2012 Jul 29. PMID:22842229 doi:10.1038/ng.2357

[4] Falk MJ, Zhang Q, Nakamaru-Ogiso E, Kannabiran C, Fonseca-Kelly Z, Chakarova C, Audo I, Mackay DS, Zeitz C, Borman AD, Staniszewska M, Shukla R, Palavalli L, Mohand-Said S, Waseem NH, Jalali S, Perin JC, Place E, Ostrovsky J, Xiao R, Bhattacharya SS, Consugar M, Webster AR, Sahel JA, Moore AT, Berson EL, Liu Q, Gai X, Pierce EA. NMNAT1 mutations cause Leber congenital amaurosis. Nat Genet. 2012 Sep;44(9):1040-5. doi: 10.1038/ng.2361. Epub 2012 Jul 29. PMID:22842227 doi:10.1038/ng.2361

[5] 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

[1]

[2]

[3]

[4]

[5]

@@ Line 1: / Line 1: @@
-{{STRUCTURE_1gzu|  PDB=1gzu  |  SCENE=  }}
-===CRYSTAL STRUCTURE OF HUMAN NICOTINAMIDE MONONUCLEOTIDE ADENYLYLTRANSFERASE IN COMPLEX WITH NMN===
-{{ABSTRACT_PUBMED_11959140}}
-==About this Structure==
+==Crystal Structure of Human Nicotinamide Mononucleotide Adenylyltransferase in Complex with NMN==
-[[1gzu]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1gry 1gry]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GZU OCA].
+<StructureSection load='1gzu' size='340' side='right'caption='[[1gzu]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
+== Structural highlights ==
-==Reference==
+<table><tr><td colspan='2'>[[1gzu]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1gry 1gry]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GZU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1GZU FirstGlance]. <br>
-<ref group="xtra">PMID:011959140</ref><references group="xtra"/><references/>
+</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=NMN:BETA-NICOTINAMIDE+RIBOSE+MONOPHOSPHATE'>NMN</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=1gzu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gzu OCA], [https://pdbe.org/1gzu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1gzu RCSB], [https://www.ebi.ac.uk/pdbsum/1gzu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1gzu ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/NMNA1_HUMAN NMNA1_HUMAN] Defects in NMNAT1 are the cause of Leber congenital amaurosis 9 (LCA9) [MIM:[https://omim.org/entry/608553 608553]. A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus.<ref>PMID:22842230</ref> <ref>PMID:22842231</ref> <ref>PMID:22842229</ref> <ref>PMID:22842227</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/NMNA1_HUMAN NMNA1_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. Also catalyzes the reverse reaction, i.e. the pyrophosphorolytic cleavage of NAD(+). For the pyrophosphorolytic activity, prefers NAD(+) and NAAD as substrates and degrades NADH, nicotinic acid adenine dinucleotide phosphate (NHD) and nicotinamide guanine dinucleotide (NGD) less effectively. Fails to cleave phosphorylated dinucleotides NADP(+), NADPH and NAADP(+). Protects against axonal degeneration following mechanical or toxic insults.<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/gz/1gzu_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=1gzu ConSurf].
+<div style="clear:both"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Nicotinamide-nucleotide adenylyltransferase]]
+[[Category: Large Structures]]
-[[Category: Heinemann, U.]]
+[[Category: Heinemann U]]
-[[Category: Lerner, F.]]
+[[Category: Lerner F]]
-[[Category: Schweiger, M.]]
+[[Category: Schweiger M]]
-[[Category: Werner, E.]]
+[[Category: Werner E]]
-[[Category: Ziegler, M.]]
+[[Category: Ziegler M]]
-[[Category: Adenylyltransferase]]
-[[Category: Nad biosynthesis]]
-[[Category: Transferase]]

1gzu: Difference between revisions

Latest revision as of 11:26, 27 March 2024

Crystal Structure of Human Nicotinamide Mononucleotide Adenylyltransferase in Complex with NMN

Structural highlights

Disease

Function

Evolutionary Conservation

References

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