2o3t: Difference between revisions
New page: left|200px<br /> <applet load="2o3t" size="450" color="white" frame="true" align="right" spinBox="true" caption="2o3t, resolution 1.68Å" /> '''Structural Basis fo... |
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[[Image:2o3t.gif|left|200px]]<br /> | [[Image:2o3t.gif|left|200px]]<br /><applet load="2o3t" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="2o3t, resolution 1.68Å" /> | caption="2o3t, resolution 1.68Å" /> | ||
'''Structural Basis for Formation and Hydrolysis of Calcium Messenger Cyclic ADP-ribose by Human CD38'''<br /> | '''Structural Basis for Formation and Hydrolysis of Calcium Messenger Cyclic ADP-ribose by Human CD38'''<br /> | ||
==Overview== | ==Overview== | ||
Human CD38 is a multifunctional ectoenzyme responsible for catalyzing the | Human CD38 is a multifunctional ectoenzyme responsible for catalyzing the conversions from nicotinamide adenine dinucleotide (NAD) to cyclic ADP-ribose (cADPR) and from cADPR to ADP-ribose (ADPR). Both cADPR and ADPR are calcium messengers that can mobilize intracellular stores and activate influx as well. In this study, we determined three crystal structures of the human CD38 enzymatic domain complexed with cADPR at 1.5-A resolution, with its analog, cyclic GDP-ribose (cGDPR) (1.68 A) and with NGD (2.1 A) a substrate analog of NAD. The results indicate that the binding of cADPR or cGDPR to the active site induces structural rearrangements in the dipeptide Glu(146)-Asp(147) by as much as 2.7 A) providing the first direct evidence of a conformational change at the active site during catalysis. In addition, Glu(226) is shown to be critical not only in catalysis but also in positioning of cADPR at the catalytic site through strong hydrogen bonding interactions. Structural details obtained from these complexes provide a step-by-step description of the catalytic processes in the synthesis and hydrolysis of cADPR. | ||
==About this Structure== | ==About this Structure== | ||
2O3T 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 CGR as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/NAD(+)_nucleosidase NAD(+) nucleosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.5 3.2.2.5] Full crystallographic information is available from [http:// | 2O3T 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 <scene name='pdbligand=CGR:'>CGR</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/NAD(+)_nucleosidase NAD(+) nucleosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.5 3.2.2.5] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2O3T OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Graeff, R.]] | [[Category: Graeff, R.]] | ||
[[Category: Hao, Q.]] | [[Category: Hao, Q.]] | ||
[[Category: Kriksunov, I | [[Category: Kriksunov, I A.]] | ||
[[Category: Lee, H | [[Category: Lee, H C.]] | ||
[[Category: Liu, Q.]] | [[Category: Liu, Q.]] | ||
[[Category: CGR]] | [[Category: CGR]] | ||
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[[Category: the catalytic pocket]] | [[Category: the catalytic pocket]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:14:08 2008'' | ||
Revision as of 19:14, 21 February 2008
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Structural Basis for Formation and Hydrolysis of Calcium Messenger Cyclic ADP-ribose by Human CD38
OverviewOverview
Human CD38 is a multifunctional ectoenzyme responsible for catalyzing the conversions from nicotinamide adenine dinucleotide (NAD) to cyclic ADP-ribose (cADPR) and from cADPR to ADP-ribose (ADPR). Both cADPR and ADPR are calcium messengers that can mobilize intracellular stores and activate influx as well. In this study, we determined three crystal structures of the human CD38 enzymatic domain complexed with cADPR at 1.5-A resolution, with its analog, cyclic GDP-ribose (cGDPR) (1.68 A) and with NGD (2.1 A) a substrate analog of NAD. The results indicate that the binding of cADPR or cGDPR to the active site induces structural rearrangements in the dipeptide Glu(146)-Asp(147) by as much as 2.7 A) providing the first direct evidence of a conformational change at the active site during catalysis. In addition, Glu(226) is shown to be critical not only in catalysis but also in positioning of cADPR at the catalytic site through strong hydrogen bonding interactions. Structural details obtained from these complexes provide a step-by-step description of the catalytic processes in the synthesis and hydrolysis of cADPR.
About this StructureAbout this Structure
2O3T is a Single protein structure of sequence from Homo sapiens with as ligand. Active as NAD(+) nucleosidase, with EC number 3.2.2.5 Full crystallographic information is available from OCA.
ReferenceReference
Structural basis for formation and hydrolysis of the calcium messenger cyclic ADP-ribose by human CD38., Liu Q, Kriksunov IA, Graeff R, Lee HC, Hao Q, J Biol Chem. 2007 Feb 23;282(8):5853-61. Epub 2006 Dec 20. PMID:17182614
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