1adf: Difference between revisions

From Proteopedia
Jump to navigationJump to search
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,328,572 edits
New page: left|200px<br /><applet load="1adf" size="450" color="white" frame="true" align="right" spinBox="true" caption="1adf, resolution 2.9Å" /> '''CRYSTALLOGRAPHIC STUD...
 
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,328,572 edits
No edit summary
 
(16 intermediate revisions by the same user not shown)
Line 1: Line 1:
[[Image:1adf.gif|left|200px]]<br /><applet load="1adf" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1adf, resolution 2.9&Aring;" />
'''CRYSTALLOGRAPHIC STUDIES OF TWO ALCOHOL DEHYDROGENASE-BOUND ANALOGS OF THIAZOLE-4-CARBOXAMIDE ADENINE DINUCLEOTIDE (TAD), THE ACTIVE ANABOLITE OF THE ANTITUMOR AGENT TIAZOFURIN'''<br />


==Overview==
==CRYSTALLOGRAPHIC STUDIES OF TWO ALCOHOL DEHYDROGENASE-BOUND ANALOGS OF THIAZOLE-4-CARBOXAMIDE ADENINE DINUCLEOTIDE (TAD), THE ACTIVE ANABOLITE OF THE ANTITUMOR AGENT TIAZOFURIN==
Thiazole-4-carboxamide adenine dinucleotide (TAD) is the active anabolite, of the antitumor drug tiazofurin. Beta-methylene TAD (beta-TAD) is a, phosphodiesterase-resistant analogue of TAD, active in, tiazofurin-resistant cells. Beta-methylene SAD (beta-SAD) is the active, selenium derivative of beta-TAD. Both agents are analogues of the cofactor, NAD and are capable of acting as general dehydrogenase inhibitors. Crystal, structures of beta-TAD and beta-SAD bound to horse liver alcohol, dehydrogenase (LADH) are presented at 2.9 and 2.7 A, respectively. Both, complexes crystallize in the orthorhombic space group C222(1) and are, isomorphous to apo-LADH. Complexes containing beta-TAD and beta-SAD were, refined to crystallographic R values of 15% and 16%, respectively, for, reflections between 8 A and the minimum d spacing. Conformations of both, inhibitors are similar. beta-TAD and beta-SAD bind to the "open" form of, LADH in the normal cofactor-binding cleft between the coenzyme and, catalytic domains of each monomer. Binding at the adenosine end of each, inhibitor resembles that of NAD. However, the positions of the thiazole, and selenazole heterocycles are displaced away from the catalytic Zn, cation by approximately 4 A. Close intramolecular S-O and Se-O contacts, observed in the parent nucleoside analogues are maintained in both, LADH-bound beta-TAD and beta-SAD, respectively. These conformational, constraints may influence the binding specificity of the inhibitors.
<StructureSection load='1adf' size='340' side='right'caption='[[1adf]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1adf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Equus_caballus Equus caballus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ADF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ADF 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]] 2.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TAD:BETA-METHYLENE-THIAZOLE-4-CARBOXYAMIDE-ADENINE+DINUCLEOTIDE'>TAD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=1adf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1adf OCA], [https://pdbe.org/1adf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1adf RCSB], [https://www.ebi.ac.uk/pdbsum/1adf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1adf ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ADH1E_HORSE ADH1E_HORSE]
== 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/ad/1adf_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=1adf ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1ADF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Equus_caballus Equus caballus] with ZN and TAD as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Alcohol_dehydrogenase Alcohol dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.1 1.1.1.1] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1ADF OCA].
*[[Alcohol dehydrogenase 3D structures|Alcohol dehydrogenase 3D structures]]
 
__TOC__
==Reference==
</StructureSection>
Crystallographic studies of two alcohol dehydrogenase-bound analogues of thiazole-4-carboxamide adenine dinucleotide (TAD), the active anabolite of the antitumor agent tiazofurin., Li H, Hallows WH, Punzi JS, Marquez VE, Carrell HL, Pankiewicz KW, Watanabe KA, Goldstein BM, Biochemistry. 1994 Jan 11;33(1):23-32. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=8286346 8286346]
[[Category: Alcohol dehydrogenase]]
[[Category: Equus caballus]]
[[Category: Equus caballus]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Carrell, H.L.]]
[[Category: Carrell HL]]
[[Category: Goldstein, B.M.]]
[[Category: Goldstein BM]]
[[Category: Hallows, W.A.]]
[[Category: Hallows WA]]
[[Category: Li, H.]]
[[Category: Li H]]
[[Category: Marquez, V.E.]]
[[Category: Marquez VE]]
[[Category: Pankiewicz, K.W.]]
[[Category: Pankiewicz KW]]
[[Category: Punzi, J.S.]]
[[Category: Punzi JS]]
[[Category: Watanabe, K.A.]]
[[Category: Watanabe KA]]
[[Category: TAD]]
[[Category: ZN]]
[[Category: oxidoreductase(nad(a)-choh(d))]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 10:46:22 2007''
Retrieved from "https://proteopedia.org/1adf"