1gs0: Difference between revisions

Revision as of 13:53, 21 February 2008

CRYSTAL STRUCTURE OF THE CATALYTIC FRAGMENT OF MURINE POLY (ADP-RIBOSE) POLYMERASE-2

OverviewOverview

Poly(ADP-ribose) polymerase-1 (PARP-1) has become an important pharmacological target in the treatment of cancer due to its cellular role as a 'DNA-strand break sensor', which leads in part to resistance to some existing chemo- and radiological treatments. Inhibitors have now been developed which prevent PARP-1 from synthesizing poly(ADP-ribose) in response to DNA-breaks and potentiate the cytotoxicity of DNA damaging agents. However, with the recent discoveries of PARP-2, which has a similar DNA-damage dependent catalytic activity, and additional members containing the 'PARP catalytic' signature, the isoform selectivity and resultant pharmacological effects of existing inhibitors are brought into question. We present here the crystal structure of the catalytic fragment of murine PARP-2, at 2.8 A resolution, and compare this to the catalytic fragment of PARP-1, with an emphasis on providing a possible framework for rational drug design in order to develop future isoform-specific inhibitors.

About this StructureAbout this Structure

1GS0 is a Single protein structure of sequence from Mus musculus. Active as NAD(+) ADP-ribosyltransferase, with EC number 2.4.2.30 Full crystallographic information is available from OCA.

ReferenceReference

Crystal structure of the catalytic fragment of murine poly(ADP-ribose) polymerase-2., Oliver AW, Ame JC, Roe SM, Good V, de Murcia G, Pearl LH, Nucleic Acids Res. 2004 Jan 22;32(2):456-64. Print 2004. PMID:14739238

Page seeded by OCA on Thu Feb 21 12:53:22 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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-[[Image:1gs0.gif|left|200px]]<br /><applet load="1gs0" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1gs0.gif|left|200px]]<br /><applet load="1gs0" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1gs0, resolution 2.80&Aring;" />
 '''CRYSTAL STRUCTURE OF THE CATALYTIC FRAGMENT OF MURINE POLY (ADP-RIBOSE) POLYMERASE-2'''<br />
 ==Overview==
-Poly(ADP-ribose) polymerase-1 (PARP-1) has become an important, pharmacological target in the treatment of cancer due to its cellular role, as a 'DNA-strand break sensor', which leads in part to resistance to some, existing chemo- and radiological treatments. Inhibitors have now been, developed which prevent PARP-1 from synthesizing poly(ADP-ribose) in, response to DNA-breaks and potentiate the cytotoxicity of DNA damaging, agents. However, with the recent discoveries of PARP-2, which has a, similar DNA-damage dependent catalytic activity, and additional members, containing the 'PARP catalytic' signature, the isoform selectivity and, resultant pharmacological effects of existing inhibitors are brought into, question. We present here the crystal structure of the catalytic fragment, of murine PARP-2, at 2.8 A resolution, and compare this to the catalytic, fragment of PARP-1, with an emphasis on providing a possible framework for, rational drug design in order to develop future isoform-specific, inhibitors.
+Poly(ADP-ribose) polymerase-1 (PARP-1) has become an important pharmacological target in the treatment of cancer due to its cellular role as a 'DNA-strand break sensor', which leads in part to resistance to some existing chemo- and radiological treatments. Inhibitors have now been developed which prevent PARP-1 from synthesizing poly(ADP-ribose) in response to DNA-breaks and potentiate the cytotoxicity of DNA damaging agents. However, with the recent discoveries of PARP-2, which has a similar DNA-damage dependent catalytic activity, and additional members containing the 'PARP catalytic' signature, the isoform selectivity and resultant pharmacological effects of existing inhibitors are brought into question. We present here the crystal structure of the catalytic fragment of murine PARP-2, at 2.8 A resolution, and compare this to the catalytic fragment of PARP-1, with an emphasis on providing a possible framework for rational drug design in order to develop future isoform-specific inhibitors.
 ==About this Structure==
-GS0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Active as [http://en.wikipedia.org/wiki/NAD(+)_ADP-ribosyltransferase NAD(+) ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.30 2.4.2.30] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1GS0 OCA].
+GS0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Active as [http://en.wikipedia.org/wiki/NAD(+)_ADP-ribosyltransferase NAD(+) ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.30 2.4.2.30] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GS0 OCA].
 ==Reference==
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 [[Category: NAD(+) ADP-ribosyltransferase]]
 [[Category: Single protein]]
-[[Category: Oliver, A.W.]]
+[[Category: Oliver, A W.]]
-[[Category: Pearl, L.H.]]
+[[Category: Pearl, L H.]]
-[[Category: Roe, S.M.]]
+[[Category: Roe, S M.]]
 [[Category: catalytic fragment]]
 [[Category: crystal structure]]
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 [[Category: polymerase transferase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 16:15:38 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:53:22 2008''