1kqo: Difference between revisions

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:1kqo.gif|left|200px]]<br />
-<applet load="1kqo" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1kqo, resolution 2.50&Aring;" />
-'''Crystal structure of NMN/NaMN adenylyltransferase complexed with deamido-NAD'''<br />
-==Overview==
+==Crystal structure of NMN/NaMN adenylyltransferase complexed with deamido-NAD==
-Nicotinamide/nicotinate mononucleotide (NMN/ NaMN)adenylyltransferase, (NMNAT) is an indispensable enzyme in the biosynthesis of NAD(+) and, NADP(+). Human NMNAT displays unique dual substrate specificity toward, both NMN and NaMN, thus flexible in participating in both de novo and, salvage pathways of NAD synthesis. Human NMNAT also catalyzes the, rate-limiting step of the metabolic conversion of the anticancer agent, tiazofurin to its active form tiazofurin adenine dinucleotide (TAD). The, tiazofurin resistance is mainly associated with the low NMNAT activity in, the cell. We have solved the crystal structures of human NMNAT in complex, with NAD, deamido-NAD, and a non-hydrolyzable TAD analogue beta-CH(2)-TAD., These complex structures delineate the broad substrate specificity of the, enzyme toward both NMN and NaMN and reveal the structural mechanism for, adenylation of tiazofurin nucleotide. The crystal structure of human NMNAT, also shows that it forms a barrel-like hexamer with the predicted nuclear, localization signal sequence located on the outside surface of the barrel, supporting its functional role of interacting with the nuclear, transporting proteins. The results from the analytical ultracentrifugation, studies are consistent with the formation of a hexamer in solution under, certain conditions.
+<StructureSection load='1kqo' size='340' side='right'caption='[[1kqo]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
+== Structural highlights ==
-==About this Structure==
+<table><tr><td colspan='2'>[[1kqo]] is a 6 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=1KQO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KQO FirstGlance]. <br>
-KQO is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with DND as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Nicotinamide-nucleotide_adenylyltransferase Nicotinamide-nucleotide adenylyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.1 2.7.7.1] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1KQO OCA].
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DND:NICOTINIC+ACID+ADENINE+DINUCLEOTIDE'>DND</scene></td></tr>
-==Reference==
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1kqo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kqo OCA], [https://pdbe.org/1kqo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1kqo RCSB], [https://www.ebi.ac.uk/pdbsum/1kqo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1kqo ProSAT]</span></td></tr>
-Structure of human nicotinamide/nicotinic acid mononucleotide adenylyltransferase. Basis for the dual substrate specificity and activation of the oncolytic agent tiazofurin., Zhou T, Kurnasov O, Tomchick DR, Binns DD, Grishin NV, Marquez VE, Osterman AL, Zhang H, J Biol Chem. 2002 Apr 12;277(15):13148-54. Epub 2002 Jan 11. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11788603 11788603]
+</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/kq/1kqo_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=1kqo ConSurf].
+<div style="clear:both"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Nicotinamide-nucleotide adenylyltransferase]]
+[[Category: Large Structures]]
-[[Category: Single protein]]
+[[Category: Binns DD]]
-[[Category: Binns, D.D.]]
+[[Category: Grishin NV]]
-[[Category: Grishin, N.V.]]
+[[Category: Kurnasov O]]
-[[Category: Kurnasov, O.]]
+[[Category: Marquez VE]]
-[[Category: Marquez, V.E.]]
+[[Category: Osterman AL]]
-[[Category: Osterman, A.L.]]
+[[Category: Tomchick DR]]
-[[Category: Tomchick, D.R.]]
+[[Category: Zhang H]]
-[[Category: Zhang, H.]]
+[[Category: Zhou T]]
-[[Category: Zhou, T.]]
-[[Category: DND]]
-[[Category: nucleotidyltransferase superfamily]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 17:53:45 2007''