1agn: Difference between revisions

Revision as of 10:14, 2 May 2008

X-RAY STRUCTURE OF HUMAN SIGMA ALCOHOL DEHYDROGENASE

OverviewOverview

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.

About this StructureAbout this Structure

1AGN is a Single protein structure of sequence from Homo sapiens. The following page contains interesting information on the relation of 1AGN with [Alcohol Dehydrogenase]. Full crystallographic information is available from OCA.

ReferenceReference

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:9228021 Page seeded by OCA on Fri May 2 10:14:38 2008

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OCA

@@ Line 1: / Line 1: @@
 [[Image:1agn.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 1agn |SIZE=350|CAPTION= <scene name='initialview01'>1agn</scene>, resolution 3.&Aring;
+The line below this paragraph, containing "STRUCTURE_1agn", creates the "Structure Box" on the page.
-|SITE= <scene name='pdbsite=ZN1:Zn+Binding+Site'>ZN1</scene>, <scene name='pdbsite=ZN2:Zn+Binding+Site'>ZN2</scene>, <scene name='pdbsite=ZN3:Zn+Binding+Site'>ZN3</scene>, <scene name='pdbsite=ZN4:Zn+Binding+Site'>ZN4</scene>, <scene name='pdbsite=ZN5:Zn+Binding+Site'>ZN5</scene>, <scene name='pdbsite=ZN6:Zn+Binding+Site'>ZN6</scene>, <scene name='pdbsite=ZN7:Zn+Binding+Site'>ZN7</scene> and <scene name='pdbsite=ZN8:Zn+Binding+Site'>ZN8</scene>
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <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>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[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] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE= HUMAN SIGMA CDNA (ADH7) ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+-->
-|DOMAIN=
+{{STRUCTURE_1agn|  PDB=1agn  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1agn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1agn OCA], [http://www.ebi.ac.uk/pdbsum/1agn PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1agn RCSB]</span>
-}}
 '''X-RAY STRUCTURE OF HUMAN SIGMA ALCOHOL DEHYDROGENASE'''
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 [[Category: Hurley, T D.]]
 [[Category: Xie, P.]]
-[[Category: oxidoreductase]]
+[[Category: Oxidoreductase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 10:14:38 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 18:39:49 2008''