View source for 2cbq


==Crystal structure of the neocarzinostatin 1Tes15 mutant bound to testosterone hemisuccinate.==
<StructureSection load='2cbq' size='340' side='right'caption='[[2cbq]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2cbq]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_carzinostaticus Streptomyces carzinostaticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CBQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CBQ 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]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TH2:TESTOSTERONE+HEMISUCCINATE'>TH2</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=2cbq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cbq OCA], [https://pdbe.org/2cbq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2cbq RCSB], [https://www.ebi.ac.uk/pdbsum/2cbq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2cbq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NCZS_STRCZ NCZS_STRCZ] NCS has antibiotic activity (for Gram-positive bacteria) and antitumor activity (for certain mouse tumors). NCS binds non-covalently to a chromophore which is the cytotoxic and mutagenic component of the antibiotic. The chromophore binds to DNA as a weak intercalator and causes single- and double-strand breaks.
== 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/cb/2cbq_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=2cbq ConSurf].
<div style="clear:both"></div>
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== Publication Abstract from PubMed ==
We have recently applied in vitro evolution methods to create in Neocarzinostatin a new binding site for a target molecule unrelated to its natural ligand. The main objective of this work was to solve the structure of some of the selected binders in complex with the target molecule: testosterone. Three proteins (1a.15, 3.24 and 4.1) were chosen as representative members of sequence families that came out of the selection process within different randomization schemes. In order to evaluate ligand-induced conformational adaptation, we also determined the structure of one of the proteins (3.24) in the free and complexed forms. Surprisingly, all these mutants bind not one but two molecules of testosterone in two very different ways. The 3.24 structure revealed that the protein spontaneously evolved in the system to bind two ligand molecules in one single binding crevice. These two binding sites are formed by substituted as well as by non-variable side-chains. The comparison with the free structure shows that only limited structural changes are observed upon ligand binding. The X-ray structures of the complex formed by 1a.15 and 4.1 Neocarzinostatin mutants revealed that the two variants form very similar dimers. These dimers were observed neither for the uncomplexed variants nor for wild-type Neocarzinostatin but were shown here to be induced by ligand binding. Comparison of the three complexed forms clearly suggests that these unanticipated structural responses resulted from the molecular arrangement used for the selection experiments.

Structures of in vitro evolved binding sites on neocarzinostatin scaffold reveal unanticipated evolutionary pathways.,Drevelle A, Graille M, Heyd B, Sorel I, Ulryck N, Pecorari F, Desmadril M, van Tilbeurgh H, Minard P J Mol Biol. 2006 Apr 28;358(2):455-71. Epub 2006 Feb 20. PMID:16529771<ref>PMID:16529771</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2cbq" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptomyces carzinostaticus]]
[[Category: Desmadril M]]
[[Category: Drevelle A]]
[[Category: Graille M]]
[[Category: Heyd B]]
[[Category: Minard P]]
[[Category: Pecorari F]]
[[Category: Sorel I]]
[[Category: Ulryck N]]
[[Category: Van Tilbeurgh H]]