View source for 3i64


==Crystal structure of an O-methyltransferase (NcsB1) from neocarzinostatin biosynthesis in complex with S-adenosyl-L-homocysteine (SAH) and 1,4-dihydroxy-2-naphthoic acid (DHN)==
<StructureSection load='3i64' size='340' side='right'caption='[[3i64]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3i64]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_carzinostaticus_subsp._neocarzinostaticus Streptomyces carzinostaticus subsp. neocarzinostaticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3I64 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3I64 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DNA:1,4-DIHYDROXY-2-NAPHTHOIC+ACID'>DNA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</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=3i64 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i64 OCA], [https://pdbe.org/3i64 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3i64 RCSB], [https://www.ebi.ac.uk/pdbsum/3i64 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3i64 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NCSB1_STRCZ NCSB1_STRCZ] S-adenosyl-L-methionine-dependent O-methyltransferase that catalyzes regiospecific methylation at the 7-hydroxy group of 2,7-dihydroxy-5-methyl-1-naphthoate in the biosynthesis of the naphthoate moiety of the neocarzinostatin chromophore. Also recognizes other dihydroxynaphthoate as substrates and catalyzes their regiospecific O-methylation. The carboxylate and its ortho-hydroxy groups of the substrate appear to be crucial for NcsB1 substrate recognition and binding, and O-methylation takes place only at the free hydroxy group of these dihydroxynaphthoic acids.<ref>PMID:18387946</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/i6/3i64_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=3i64 ConSurf].
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== Publication Abstract from PubMed ==
The small molecule component of the chromoprotein enediyne antitumor antibiotics is biosynthesized through a convergent route, incorporating amino acid, polyketide and carbohydrate building blocks around a central enediyne hydrocarbon core. The naphthoic acid moiety of the enediyne neocarzinostatin plays key roles in the biological activity of the natural product by interacting with both the carrier protein and duplex DNA at the site of action. We have previously described the in vitro characterization of an S-adenosylmethionine-dependent O-methyltransferase (NcsB1) in the neocarzinostatin biosynthetic pathway (Luo, Y.; Lin, S.; Zhang, J.; Cooke, H. A.; Bruner, S. D. and Shen, B. (2008) J. Biol. Chem. 283, 14694-14702). Here we provide a structural basis for NcsB1 activity, illustrating that the enzyme shares an overall architecture with a large family of S-adenosylmethionine-dependent proteins. In addition, NcsB1 represents the first enzyme to be structurally characterized in the biosynthetic pathway of neocarzinostatin. By co-crystallizing the enzyme with various combinations of the cofactor and substrate analogs, details of the active site structure have been established. Changes in subdomain orientation were observed by comparing structures in the presence and absence of substrate, suggesting that reorientation of the enzyme is involved in binding the substrate. In addition, residues important for substrate discrimination were predicted and probed through site directed mutagenesis and in vitro biochemical characterization.

Molecular basis of substrate promiscuity for the SAM-dependent O-methyltransferase NcsB1, involved in the biosynthesis of the enediyne antitumor antibiotic neocarzinostatin.,Cooke HA, Guenther EL, Luo Y, Shen B, Bruner SD Biochemistry. 2009 Aug 25. PMID:19702337<ref>PMID:19702337</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptomyces carzinostaticus subsp. neocarzinostaticus]]
[[Category: Bruner SD]]
[[Category: Cooke HA]]