1u3t

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{{Seed}}
 
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[[Image:1u3t.png|left|200px]]
 
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==Crystal Structure of Human Alcohol Dehydrogenase Alpha-Alpha Isoform Complexed with N-Cyclopentyl-N-Cyclobutylformamide Determined to 2.5 Angstrom Resolution==
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The line below this paragraph, containing "STRUCTURE_1u3t", creates the "Structure Box" on the page.
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<StructureSection load='1u3t' size='340' side='right'caption='[[1u3t]], [[Resolution|resolution]] 2.49&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1u3t]] is a 2 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=1U3T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1U3T FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.49&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CCB:CYCLOBUTYL(CYCLOPENTYL)FORMAMIDE'>CCB</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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{{STRUCTURE_1u3t| PDB=1u3t | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1u3t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u3t OCA], [https://pdbe.org/1u3t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1u3t RCSB], [https://www.ebi.ac.uk/pdbsum/1u3t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1u3t ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/ADH1A_HUMAN ADH1A_HUMAN]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/u3/1u3t_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1u3t ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Formamides are aldehyde analogues that have demonstrated potent and selective inhibition of human alcohol dehydrogenase isoenzymes. The alphaalpha, beta(1)beta(1), gamma(2)gamma(2), and sigmasigma isoforms have all been found to be strongly inhibited by substituted formamides. In this paper, the structure of the alphaalpha isoform of human alcohol dehydrogenase complexed with N-cyclopentyl-N-cyclobutylformamide was determined by X-ray crystallography to 2.5 A resolution, the beta(1)beta(1) isoform of human alcohol dehydrogenase complexed with N-benzylformamide and with N-heptylformamide was determined to 1.6 and 1.65 A resolution, respectively, and the structure of the gamma(2)gamma(2) isoform complexed with N-1-methylheptylformamide was determined to 1.45 A resolution. These structures provide the first substrate-level view of the local structural differences that give rise to the individual substrate preferences shown by these highly related isoenzymes. Consistent with previous work, the carbonyl oxygen of the inhibitors interacts directly with the catalytic zinc and the hydroxyl group of Thr48 (Ser48 for gamma(2)gamma(2)) of the enzyme. The benzene ring of N-benzylformamide and the carbon chains of N-heptylformamide and N-1-methylheptylformamide interact with the sides of the hydrophobic substrate pocket whose size and shape is dictated by residue exchanges between the beta(1)beta(1) and gamma(2)gamma(2) isoenzymes. In particular, the exchange of Ser for Thr at position 48 and the exchange of Val for Leu at position 141 in the gamma(2)gamma(2) isoenzyme create an environment with stereoselectivity for the R-enantiomer of the branched N-1-methylheptylformamide inhibitor in this isoenzyme. The primary feature of the alphaalpha isoform is the Ala for Phe93 exchange that enlarges the active site near the catalytic zinc and creates the specificity for the branched N-cyclopentyl-N-cyclobutylformamide inhibitor, which shows the greatest selectivity for this unique isoenzyme of any of the formamide inhibitors.
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===Crystal Structure of Human Alcohol Dehydrogenase Alpha-Alpha Isoform Complexed with N-Cyclopentyl-N-Cyclobutylformamide Determined to 2.5 Angstrom Resolution===
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Structure of three class I human alcohol dehydrogenases complexed with isoenzyme specific formamide inhibitors.,Gibbons BJ, Hurley TD Biochemistry. 2004 Oct 5;43(39):12555-62. PMID:15449945<ref>PMID:15449945</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 1u3t" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_15449945}}, adds the Publication Abstract to the page
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*[[Alcohol dehydrogenase 3D structures|Alcohol dehydrogenase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 15449945 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_15449945}}
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__TOC__
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</StructureSection>
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==About this Structure==
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1U3T is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1U3T OCA].
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==Reference==
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Structure of three class I human alcohol dehydrogenases complexed with isoenzyme specific formamide inhibitors., Gibbons BJ, Hurley TD, Biochemistry. 2004 Oct 5;43(39):12555-62. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15449945 15449945]
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[[Category: Alcohol dehydrogenase]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Gibbons, B J.]]
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[[Category: Gibbons BJ]]
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[[Category: Hurley, T D.]]
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[[Category: Hurley TD]]
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[[Category: Oxidoreductase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 18:53:03 2008''
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Current revision

Crystal Structure of Human Alcohol Dehydrogenase Alpha-Alpha Isoform Complexed with N-Cyclopentyl-N-Cyclobutylformamide Determined to 2.5 Angstrom Resolution

PDB ID 1u3t

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