2o2r
From Proteopedia
(New page: 200px<br /><applet load="2o2r" size="450" color="white" frame="true" align="right" spinBox="true" caption="2o2r, resolution 2.20Å" /> '''Crystal structure of...) |
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| - | [[Image:2o2r.jpg|left|200px]]<br /><applet load="2o2r" size=" | + | [[Image:2o2r.jpg|left|200px]]<br /><applet load="2o2r" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2o2r, resolution 2.20Å" /> | caption="2o2r, resolution 2.20Å" /> | ||
'''Crystal structure of the C-terminal domain of rat 10'formyltetrahydrofolate dehydrogenase in complex with NADPH'''<br /> | '''Crystal structure of the C-terminal domain of rat 10'formyltetrahydrofolate dehydrogenase in complex with NADPH'''<br /> | ||
==Overview== | ==Overview== | ||
| - | 10-Formyltetrahydrofolate dehydrogenase (FDH) catalyzes an NADP+-dependent | + | 10-Formyltetrahydrofolate dehydrogenase (FDH) catalyzes an NADP+-dependent dehydrogenase reaction resulting in conversion of 10-formyltetrahydrofolate to tetrahydrofolate and CO2. This reaction is a result of the concerted action of two catalytic domains of FDH, the amino-terminal hydrolase domain and the carboxyl-terminal aldehyde dehydrogenase domain. In addition to participation in the overall FDH mechanism, the C-terminal domain is capable of NADP+-dependent oxidation of short chain aldehydes to their corresponding acids. We have determined the crystal structure of the C-terminal domain of FDH and its complexes with oxidized and reduced forms of NADP. Compared to other members of the ALDH family, FDH demonstrates a new mode of binding of the 2'-phosphate group of NADP via a water-mediated contact with Gln600 that may contribute to the specificity of the enzyme for NADP over NAD. The structures also suggest how Glu673 can act as a general base in both acylation and deacylation steps of the reaction. In the apo structure, the general base Glu673 is positioned optimally for proton abstraction from the sulfur atom of Cys707. Upon binding of NADP+, the side chain of Glu673 is displaced from the active site by the nicotinamide ring and contacts a chain of highly ordered water molecules that may represent a pathway for translocation of the abstracted proton from Glu673 to the solvent. When reduced, the nicotinamide ring of NADP is displaced from the active site, restoring the contact between Cys707 and Glu673 and allowing the latter to activate the hydrolytic water molecule in deacylation. |
==About this Structure== | ==About this Structure== | ||
| - | 2O2R is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with SO4, NDP and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Formyltetrahydrofolate_dehydrogenase Formyltetrahydrofolate dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.6 1.5.1.6] Full crystallographic information is available from [http:// | + | 2O2R is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=NDP:'>NDP</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Formyltetrahydrofolate_dehydrogenase Formyltetrahydrofolate dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.6 1.5.1.6] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2O2R OCA]. |
==Reference== | ==Reference== | ||
| - | Crystal | + | Crystal structures of the carboxyl terminal domain of rat 10-formyltetrahydrofolate dehydrogenase: implications for the catalytic mechanism of aldehyde dehydrogenases., Tsybovsky Y, Donato H, Krupenko NI, Davies C, Krupenko SA, Biochemistry. 2007 Mar 20;46(11):2917-29. Epub 2007 Feb 16. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17302434 17302434] |
[[Category: Formyltetrahydrofolate dehydrogenase]] | [[Category: Formyltetrahydrofolate dehydrogenase]] | ||
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
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[[Category: Davies, C.]] | [[Category: Davies, C.]] | ||
[[Category: Donato, H.]] | [[Category: Donato, H.]] | ||
| - | [[Category: Krupenko, N | + | [[Category: Krupenko, N I.]] |
| - | [[Category: Krupenko, S | + | [[Category: Krupenko, S A.]] |
[[Category: Tsybovsky, Y.]] | [[Category: Tsybovsky, Y.]] | ||
[[Category: GOL]] | [[Category: GOL]] | ||
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[[Category: fdh]] | [[Category: fdh]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:13:48 2008'' |
Revision as of 16:13, 21 February 2008
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Crystal structure of the C-terminal domain of rat 10'formyltetrahydrofolate dehydrogenase in complex with NADPH
Overview
10-Formyltetrahydrofolate dehydrogenase (FDH) catalyzes an NADP+-dependent dehydrogenase reaction resulting in conversion of 10-formyltetrahydrofolate to tetrahydrofolate and CO2. This reaction is a result of the concerted action of two catalytic domains of FDH, the amino-terminal hydrolase domain and the carboxyl-terminal aldehyde dehydrogenase domain. In addition to participation in the overall FDH mechanism, the C-terminal domain is capable of NADP+-dependent oxidation of short chain aldehydes to their corresponding acids. We have determined the crystal structure of the C-terminal domain of FDH and its complexes with oxidized and reduced forms of NADP. Compared to other members of the ALDH family, FDH demonstrates a new mode of binding of the 2'-phosphate group of NADP via a water-mediated contact with Gln600 that may contribute to the specificity of the enzyme for NADP over NAD. The structures also suggest how Glu673 can act as a general base in both acylation and deacylation steps of the reaction. In the apo structure, the general base Glu673 is positioned optimally for proton abstraction from the sulfur atom of Cys707. Upon binding of NADP+, the side chain of Glu673 is displaced from the active site by the nicotinamide ring and contacts a chain of highly ordered water molecules that may represent a pathway for translocation of the abstracted proton from Glu673 to the solvent. When reduced, the nicotinamide ring of NADP is displaced from the active site, restoring the contact between Cys707 and Glu673 and allowing the latter to activate the hydrolytic water molecule in deacylation.
About this Structure
2O2R is a Single protein structure of sequence from Rattus norvegicus with , and as ligands. Active as Formyltetrahydrofolate dehydrogenase, with EC number 1.5.1.6 Full crystallographic information is available from OCA.
Reference
Crystal structures of the carboxyl terminal domain of rat 10-formyltetrahydrofolate dehydrogenase: implications for the catalytic mechanism of aldehyde dehydrogenases., Tsybovsky Y, Donato H, Krupenko NI, Davies C, Krupenko SA, Biochemistry. 2007 Mar 20;46(11):2917-29. Epub 2007 Feb 16. PMID:17302434
Page seeded by OCA on Thu Feb 21 18:13:48 2008
