1r12: Difference between revisions

Revision as of 15:45, 21 February 2008

Native Aplysia ADP ribosyl cyclase

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

1R12 is a Single protein structure of sequence from Aplysia californica. Active as NAD(+) nucleosidase, with EC number 3.2.2.5 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

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OCA

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-[[Image:1r12.jpg|left|200px]]<br /><applet load="1r12" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1r12.jpg|left|200px]]<br /><applet load="1r12" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1r12, resolution 1.7&Aring;" />
 '''Native Aplysia ADP ribosyl cyclase'''<br />
 ==Overview==
-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.
+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 Structure==
-R12 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Aplysia_californica Aplysia californica]. 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1R12 OCA].
+R12 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Aplysia_californica Aplysia californica]. 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=1R12 OCA].
 ==Reference==
@@ Line 16: / Line 16: @@
 [[Category: Graeff, R.]]
 [[Category: Hao, Q.]]
-[[Category: Kriksunov, I.A.]]
+[[Category: Kriksunov, I A.]]
-[[Category: Lee, H.C.]]
+[[Category: Lee, H C.]]
-[[Category: Love, M.L.]]
+[[Category: Love, M L.]]
 [[Category: Munshi, C.]]
-[[Category: Szebenyi, D.M.E.]]
+[[Category: Szebenyi, D M.E.]]
-[[Category: Thiel, D.J.]]
+[[Category: Thiel, D J.]]
 [[Category: adp-ribosyl cyclase]]
 [[Category: ca2+ signalling]]
@@ Line 28: / Line 28: @@
 [[Category: x-ray crystallography]]
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