1kqo: Difference between revisions
Jump to navigation
Jump to search
m Protected "1kqo" [edit=sysop:move=sysop] |
No edit summary |
||
| Line 1: | Line 1: | ||
{{STRUCTURE_1kqo| PDB=1kqo | SCENE= }} | {{STRUCTURE_1kqo| PDB=1kqo | SCENE= }} | ||
===Crystal structure of NMN/NaMN adenylyltransferase complexed with deamido-NAD=== | |||
{{ABSTRACT_PUBMED_11788603}} | |||
=== | ==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> | |||
==About this Structure== | ==About this Structure== | ||
| Line 11: | Line 13: | ||
==Reference== | ==Reference== | ||
<ref group="xtra">PMID:011788603</ref><ref group="xtra">PMID:011959140</ref><references group="xtra"/> | <ref group="xtra">PMID:011788603</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]] | ||
Revision as of 21:14, 24 March 2013
Crystal structure of NMN/NaMN adenylyltransferase complexed with deamido-NADCrystal structure of NMN/NaMN adenylyltransferase complexed with deamido-NAD
Template:ABSTRACT PUBMED 11788603
DiseaseDisease
[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]
FunctionFunction
[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 StructureAbout this Structure
1kqo is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
- ↑ Zhou T, Kurnasov O, Tomchick DR, Binns DD, Grishin NV, Marquez VE, Osterman AL, Zhang H. Structure of human nicotinamide/nicotinic acid mononucleotide adenylyltransferase. Basis for the dual substrate specificity and activation of the oncolytic agent tiazofurin. J Biol Chem. 2002 Apr 12;277(15):13148-54. Epub 2002 Jan 11. PMID:11788603 doi:10.1074/jbc.M111469200
- ↑ 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