1r0s: Difference between revisions

Revision as of 06:56, 3 May 2008

Crystal structure of ADP-ribosyl cyclase Glu179Ala mutant

OverviewOverview

ADP-ribosyl cyclase catalyzes the elimination of nicotinamide from NAD and cyclization to cADPR, a known second messenger in cellular calcium signaling pathways. We have determined to 2.0 A resolution the structure of Aplysia cyclase with ribose-5-phosphate bound covalently at C3' and with the base exchange substrate (BES), pyridylcarbinol, bound to the active site. In addition, further refinement at 2.4 A resolution of the structure of nicotinamide-bound cyclase, which was previously reported, reveals that ribose-5-phosphate is also covalently bound in this structure, and a second nicotinamide site was identified. The structures of native and mutant Glu179Ala cyclase were also solved to 1.7 and 2.0 A respectively. It is proposed that the second nicotinamide site serves to promote cyclization by clearing the active site of the nicotinamide byproduct. Moreover, a ribosylation mechanism can be proposed in which the cyclization reaction proceeds through a covalently bound intermediate.

About this StructureAbout this Structure

1R0S is a Single protein structure of sequence from Aplysia californica. Full crystallographic information is available from OCA.

ReferenceReference

ADP-ribosyl cyclase; crystal structures reveal a covalent intermediate., Love ML, Szebenyi DM, Kriksunov IA, Thiel DJ, Munshi C, Graeff R, Lee HC, Hao Q, Structure. 2004 Mar;12(3):477-86. PMID:15016363 Page seeded by OCA on Sat May 3 06:56:06 2008

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OCA

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 [[Image:1r0s.jpg|left|200px]]
- {{Structure
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-|ACTIVITY= <span class='plainlinks'>[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] </span>
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-}}
 '''Crystal structure of ADP-ribosyl cyclase Glu179Ala mutant'''
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 ADP-ribosyl cyclase; crystal structures reveal a covalent intermediate., Love ML, Szebenyi DM, Kriksunov IA, Thiel DJ, Munshi C, Graeff R, Lee HC, Hao Q, Structure. 2004 Mar;12(3):477-86. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15016363 15016363]
 [[Category: Aplysia californica]]
-[[Category: NAD(+) nucleosidase]]
 [[Category: Single protein]]
 [[Category: Graeff, R.]]
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 [[Category: Szebenyi, D M.E.]]
 [[Category: Thiel, D J.]]
-[[Category: adp-ribosyl cyclase]]
+[[Category: Adp-ribosyl cyclase]]
-[[Category: ca2+ signalling]]
+[[Category: Ca2+ signalling]]
-[[Category: cyclic adp-ribose]]
+[[Category: Cyclic adp-ribose]]
-[[Category: naadp]]
+[[Category: Naadp]]
-[[Category: x-ray crystallography]]
+[[Category: X-ray crystallography]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 06:56:06 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:21:38 2008''