1agn: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older edit
No edit summary
No edit summary
 
(21 intermediate revisions by the same user not shown)
Line 1: Line 1:
[[Image:1agn.gif|left|200px]]<br />
<applet load="1agn" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1agn, resolution 3.&Aring;" />
'''X-RAY STRUCTURE OF HUMAN SIGMA ALCOHOL DEHYDROGENASE'''<br />


==Overview==
==X-RAY STRUCTURE OF HUMAN SIGMA ALCOHOL DEHYDROGENASE==
The structural determinants of substrate recognition in the human class, IV, or sigmasigma, alcohol dehydrogenase (ADH) isoenzyme were examined, through x-ray crystallography and site-directed mutagenesis. The crystal, structure of sigmasigma ADH complexed with NAD+ and acetate was solved to, 3-A resolution. The human beta1beta1 and sigmasigma ADH isoenzymes share, 69% sequence identity and exhibit dramatically different kinetic, properties. Differences in the amino acids at positions 57, 116, 141, 309, and 317 create a different topology within the sigmasigma, substrate-binding pocket, relative to the beta1beta1 isoenzyme. The, nicotinamide ring of the NAD(H) molecule, in the sigmasigma structure, appears to be twisted relative to its position in the beta1beta1, isoenzyme. In conjunction with movements of Thr-48 and Phe-93, this twist, widens the substrate pocket in the vicinity of the catalytic zinc and may, contribute to this isoenzyme's high Km for small substrates. The presence, of Met-57, Met-141, and Phe-309 narrow the middle region of the sigmasigma, substrate pocket and may explain the substantially decreased Km values, with increased chain length of substrates in sigmasigma ADH. The kinetic, properties of a mutant sigmasigma enzyme (sigma309L317A) suggest that, widening the middle region of the substrate pocket increases Km by, weakening the interactions between the enzyme and smaller substrates while, not affecting the binding of longer alcohols, such as hexanol and retinol.
<StructureSection load='1agn' size='340' side='right'caption='[[1agn]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1agn]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The January 2001 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Alcohol Dehydrogenase''  by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2001_1 10.2210/rcsb_pdb/mom_2001_1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AGN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1AGN 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=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</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=1agn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1agn OCA], [https://pdbe.org/1agn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1agn RCSB], [https://www.ebi.ac.uk/pdbsum/1agn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1agn ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ADH7_HUMAN ADH7_HUMAN] Could function in retinol oxidation for the synthesis of retinoic acid, a hormone important for cellular differentiation. Medium-chain (octanol) and aromatic (m-nitrobenzaldehyde) compounds are the best substrates. Ethanol is not a good substrate but at the high ethanol concentrations reached in the digestive tract, it plays a role in the ethanol oxidation and contributes to the first pass ethanol metabolism.
== 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/ag/1agn_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=1agn ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1AGN is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN, ACT and NAD as [http://en.wikipedia.org/wiki/ligands ligands]. The following page contains interesting information on the relation of 1AGN with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb13_1.html Alcohol Dehydrogenase]]. 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] Structure known Active Sites: ZN1, ZN2, ZN3, ZN4, ZN5, ZN6, ZN7 and ZN8. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1AGN OCA].
*[[Alcohol dehydrogenase 3D structures|Alcohol dehydrogenase 3D structures]]
 
__TOC__
==Reference==
</StructureSection>
X-ray structure of human class IV sigmasigma alcohol dehydrogenase. Structural basis for substrate specificity., Xie P, Parsons SH, Speckhard DC, Bosron WF, Hurley TD, J Biol Chem. 1997 Jul 25;272(30):18558-63. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9228021 9228021]
[[Category: Alcohol Dehydrogenase]]
[[Category: Alcohol Dehydrogenase]]
[[Category: Alcohol dehydrogenase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Hurley, T.D.]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: Xie, P.]]
[[Category: Hurley TD]]
[[Category: ACT]]
[[Category: Xie P]]
[[Category: NAD]]
[[Category: ZN]]
[[Category: oxidoreductase]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 15:58:23 2007''

Latest revision as of 09:30, 7 February 2024

X-RAY STRUCTURE OF HUMAN SIGMA ALCOHOL DEHYDROGENASEX-RAY STRUCTURE OF HUMAN SIGMA ALCOHOL DEHYDROGENASE

Structural highlights

1agn is a 4 chain structure with sequence from Homo sapiens. The January 2001 RCSB PDB Molecule of the Month feature on Alcohol Dehydrogenase by David S. Goodsell is 10.2210/rcsb_pdb/mom_2001_1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ADH7_HUMAN Could function in retinol oxidation for the synthesis of retinoic acid, a hormone important for cellular differentiation. Medium-chain (octanol) and aromatic (m-nitrobenzaldehyde) compounds are the best substrates. Ethanol is not a good substrate but at the high ethanol concentrations reached in the digestive tract, it plays a role in the ethanol oxidation and contributes to the first pass ethanol metabolism.

Evolutionary Conservation

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

See Also

1agn, resolution 3.00Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=1agn&oldid=4040124"