1ps0: Difference between revisions

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Crystal Structure of the NADP(H)-Dependent Cinnamyl Alcohol Dehydrogenase from Saccharomyces cerevisiae

OverviewOverview

The crystal structure of Saccharomyces cerevisiae ScAdh6p has been solved using the anomalous signal from the two zinc atoms found per subunit, and it constitutes the first structure determined from a member of the cinnamyl alcohol dehydrogenase family. ScAdh6p subunits exhibit the general fold of the medium-chain dehydrogenases/reductases (MDR) but with distinct specific characteristics. In the three crystal structures solved (two trigonal and one monoclinic), ScAdh6p molecules appear to be structural heterodimers composed of one subunit in the apo and the second subunit in the holo conformation. Between the two conformations, the relative disposition of domains remains unchanged, while two loops, Cys250-Asn260 and Ile277-Lys292, experience large movements. The apo-apo structure is disfavoured because of steric impairment involving the loop Ile277-Lys292, while in the holo-holo conformation some of the hydrogen bonds between subunits would break apart. These suggest that the first NADPH molecule would bind to the enzyme much more tightly than the second. In addition, fluorimetric analysis of NADPH binding demonstrates that only one cofactor molecule binds per dimer. Therefore, ScAdh6p appears to function according to a half-of-the-sites reactivity mechanism, resulting from a pre-existing (prior to cofactor binding) tendency for the structural asymmetry in the dimer. The specificity of ScAdh6p towards NADPH is mainly due to the tripod-like interactions of the terminal phosphate group with Ser210, Arg211 and Lys215. The size and the shape of the substrate-binding pocket correlate well with the substrate specificity of ScAdh6p towards cinnamaldehyde and other aromatic compounds. The structural relationships of ScAdh6p with other MDR structures are analysed.

About this StructureAbout this Structure

1PS0 is a Single protein structure of sequence from Saccharomyces cerevisiae with and as ligands. Full crystallographic information is available from OCA.

ReferenceReference

Apo and Holo structures of an NADPH-dependent cinnamyl alcohol dehydrogenase from Saccharomyces cerevisiae., Valencia E, Larroy C, Ochoa WF, Pares X, Fita I, Biosca JA, J Mol Biol. 2004 Aug 20;341(4):1049-62. PMID:15289102

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-[[Image:1ps0.gif|left|200px]]<br /><applet load="1ps0" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1ps0.gif|left|200px]]<br /><applet load="1ps0" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1ps0, resolution 3.01&Aring;" />
 '''Crystal Structure of the NADP(H)-Dependent Cinnamyl Alcohol Dehydrogenase from Saccharomyces cerevisiae'''<br />
 ==Overview==
-The crystal structure of Saccharomyces cerevisiae ScAdh6p has been solved, using the anomalous signal from the two zinc atoms found per subunit, and, it constitutes the first structure determined from a member of the, cinnamyl alcohol dehydrogenase family. ScAdh6p subunits exhibit the, general fold of the medium-chain dehydrogenases/reductases (MDR) but with, distinct specific characteristics. In the three crystal structures solved, (two trigonal and one monoclinic), ScAdh6p molecules appear to be, structural heterodimers composed of one subunit in the apo and the second, subunit in the holo conformation. Between the two conformations, the, relative disposition of domains remains unchanged, while two loops, Cys250-Asn260 and Ile277-Lys292, experience large movements. The apo-apo, structure is disfavoured because of steric impairment involving the loop, Ile277-Lys292, while in the holo-holo conformation some of the hydrogen, bonds between subunits would break apart. These suggest that the first, NADPH molecule would bind to the enzyme much more tightly than the second., In addition, fluorimetric analysis of NADPH binding demonstrates that only, one cofactor molecule binds per dimer. Therefore, ScAdh6p appears to, function according to a half-of-the-sites reactivity mechanism, resulting, from a pre-existing (prior to cofactor binding) tendency for the, structural asymmetry in the dimer. The specificity of ScAdh6p towards, NADPH is mainly due to the tripod-like interactions of the terminal, phosphate group with Ser210, Arg211 and Lys215. The size and the shape of, the substrate-binding pocket correlate well with the substrate specificity, of ScAdh6p towards cinnamaldehyde and other aromatic compounds. The, structural relationships of ScAdh6p with other MDR structures are, analysed.
+The crystal structure of Saccharomyces cerevisiae ScAdh6p has been solved using the anomalous signal from the two zinc atoms found per subunit, and it constitutes the first structure determined from a member of the cinnamyl alcohol dehydrogenase family. ScAdh6p subunits exhibit the general fold of the medium-chain dehydrogenases/reductases (MDR) but with distinct specific characteristics. In the three crystal structures solved (two trigonal and one monoclinic), ScAdh6p molecules appear to be structural heterodimers composed of one subunit in the apo and the second subunit in the holo conformation. Between the two conformations, the relative disposition of domains remains unchanged, while two loops, Cys250-Asn260 and Ile277-Lys292, experience large movements. The apo-apo structure is disfavoured because of steric impairment involving the loop Ile277-Lys292, while in the holo-holo conformation some of the hydrogen bonds between subunits would break apart. These suggest that the first NADPH molecule would bind to the enzyme much more tightly than the second. In addition, fluorimetric analysis of NADPH binding demonstrates that only one cofactor molecule binds per dimer. Therefore, ScAdh6p appears to function according to a half-of-the-sites reactivity mechanism, resulting from a pre-existing (prior to cofactor binding) tendency for the structural asymmetry in the dimer. The specificity of ScAdh6p towards NADPH is mainly due to the tripod-like interactions of the terminal phosphate group with Ser210, Arg211 and Lys215. The size and the shape of the substrate-binding pocket correlate well with the substrate specificity of ScAdh6p towards cinnamaldehyde and other aromatic compounds. The structural relationships of ScAdh6p with other MDR structures are analysed.
 ==About this Structure==
-PS0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with ZN and NAP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1PS0 OCA].
+PS0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=NAP:'>NAP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PS0 OCA].
 ==Reference==
@@ Line 13: / Line 13: @@
 [[Category: Saccharomyces cerevisiae]]
 [[Category: Single protein]]
-[[Category: Biosca, J.A.]]
+[[Category: Biosca, J A.]]
 [[Category: Fita, I.]]
 [[Category: Larroy, C.]]
-[[Category: Ochoa, W.F.]]
+[[Category: Ochoa, W F.]]
 [[Category: Pares, X.]]
 [[Category: Valencia, E.]]
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 [[Category: nadp(h)dependent]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 00:04:20 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:31:55 2008''