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3i53

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Revision as of 09:30, 19 December 2018

Crystal structure of an O-methyltransferase (NcsB1) from neocarzinostatin biosynthesis in complex with S-adenosyl-L-homocysteine (SAH)

Structural highlights

3i53 is a 2 chain structure with sequence from "streptomyces_carzinostaticus_subsp._neocarzinostaticus"_ishida_et_al. "streptomyces carzinostaticus subsp. neocarzinostaticus" ishida et al.. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	3i58, 3i5u, 3i64
Gene:	ncsb1 ("Streptomyces carzinostaticus subsp. neocarzinostaticus" Ishida et al.)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1]

Evolutionary Conservation

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

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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Luo Y, Lin S, Zhang J, Cooke HA, Bruner SD, Shen B. Regiospecific O-methylation of naphthoic acids catalyzed by NcsB1, an O-methyltransferase involved in the biosynthesis of the enediyne antitumor antibiotic neocarzinostatin. J Biol Chem. 2008 May 23;283(21):14694-702. doi: 10.1074/jbc.M802206200. Epub, 2008 Apr 3. PMID:18387946 doi:http://dx.doi.org/10.1074/jbc.M802206200
↑ Cooke HA, Guenther EL, Luo Y, Shen B, Bruner SD. Molecular basis of substrate promiscuity for the SAM-dependent O-methyltransferase NcsB1, involved in the biosynthesis of the enediyne antitumor antibiotic neocarzinostatin. Biochemistry. 2009 Aug 25. PMID:19702337 doi:10.1021/bi901257q

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3i53"

@@ Line 1: / Line 1: @@
 ==Crystal structure of an O-methyltransferase (NcsB1) from neocarzinostatin biosynthesis in complex with S-adenosyl-L-homocysteine (SAH)==
 <StructureSection load='3i53' size='340' side='right' caption='[[3i53]], [[Resolution|resolution]] 2.08&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3i58|3i58]], [[3i5u|3i5u]], [[3i64|3i64]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ncsb1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=167636 "Streptomyces carzinostaticus subsp. neocarzinostaticus" Ishida et al.])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3i53 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i53 OCA], [http://pdbe.org/3i53 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3i53 RCSB], [http://www.ebi.ac.uk/pdbsum/3i53 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3i53 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i53 OCA], [http://pdbe.org/3i53 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3i53 RCSB], [http://www.ebi.ac.uk/pdbsum/3i53 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3i53 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 14: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i5/3i53_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i5/3i53_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

3i53

From Proteopedia

Revision as of 09:30, 19 December 2018

Crystal structure of an O-methyltransferase (NcsB1) from neocarzinostatin biosynthesis in complex with S-adenosyl-L-homocysteine (SAH)

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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