1kku
From Proteopedia
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{{STRUCTURE_1kku| PDB=1kku | SCENE= }} | {{STRUCTURE_1kku| PDB=1kku | SCENE= }} | ||
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===Crystal structure of nuclear human nicotinamide mononucleotide adenylyltransferase=== | ===Crystal structure of nuclear human nicotinamide mononucleotide adenylyltransferase=== | ||
| + | {{ABSTRACT_PUBMED_11751893}} | ||
| + | ==Disease== | ||
| + | [[http://www.uniprot.org/uniprot/NMNA1_HUMAN NMNA1_HUMAN]] Defects in NMNAT1 are the cause of Leber congenital amaurosis 9 (LCA9) [MIM:[http://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== | |
| - | + | [[http://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> | |
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==About this Structure== | ==About this Structure== | ||
| - | + | [[1kku]] is a 1 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=1KKU OCA]. | |
==Reference== | ==Reference== | ||
| - | <ref group="xtra">PMID: | + | <ref group="xtra">PMID:011751893</ref><ref group="xtra">PMID:011959140</ref><references group="xtra"/><references/> |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Nicotinamide-nucleotide adenylyltransferase]] | [[Category: Nicotinamide-nucleotide adenylyltransferase]] | ||
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[[Category: Rizzi, M.]] | [[Category: Rizzi, M.]] | ||
[[Category: Alpha/beta structure - rossmann fold]] | [[Category: Alpha/beta structure - rossmann fold]] | ||
| - | + | [[Category: Transferase]] | |
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Revision as of 03:54, 25 March 2013
Contents |
Crystal structure of nuclear human nicotinamide mononucleotide adenylyltransferase
Template:ABSTRACT PUBMED 11751893
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]
About this Structure
1kku is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
- Garavaglia S, D'Angelo I, Emanuelli M, Carnevali F, Pierella F, Magni G, Rizzi M. Structure of human NMN adenylyltransferase. A key nuclear enzyme for NAD homeostasis. J Biol Chem. 2002 Mar 8;277(10):8524-30. Epub 2001 Dec 19. PMID:11751893 doi:10.1074/jbc.M111589200
- Werner E, Ziegler M, Lerner F, Schweiger M, Heinemann U. Crystal structure of human nicotinamide mononucleotide adenylyltransferase in complex with NMN. FEBS Lett. 2002 Apr 10;516(1-3):239-44. PMID:11959140
- ↑ 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
