1o0f: Difference between revisions

Revision as of 15:12, 21 February 2008

RNASE A in complex with 3',5'-ADP

OverviewOverview

The crystal structures of bovine pancreatic ribonuclease A (RNase A) in complex with 3',5'-ADP, 2',5'-ADP, 5'-ADP, U-2'-p and U-3'-p have been determined at high resolution. The structures reveal that each inhibitor binds differently in the RNase A active site by anchoring a phosphate group in subsite P1. The most potent inhibitor of all five, 5'-ADP (Ki = 1.2 microM), adopts a syn conformation (in contrast to 3',5'-ADP and 2',5'-ADP, which adopt an anti), and it is the beta- rather than the alpha-phosphate group that binds to P1. 3',5'-ADP binds with the 5'-phosphate group in P1 and the adenosine in the B2 pocket. Two different binding modes are observed in the two RNase A molecules of the asymmetric unit for 2',5'-ADP. This inhibitor binds with either the 3' or the 5' phosphate groups in subsite P1, and in each case, the adenosine binds in two different positions within the B2 subsite. The two uridilyl inhibitors bind similarly with the uridine moiety in the B1 subsite but the placement of a different phosphate group in P1 (2' versus 3') has significant implications on their potency against RNase A. Comparative structural analysis of the RNase A, eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP), and human angiogenin (Ang) complexes with these and other phosphonucleotide inhibitors provides a wealth of information for structure-based design of inhibitors specific for each RNase. These inhibitors could be developed to therapeutic agents that could control the biological activities of EDN, ECP, and ANG, which play key roles in human pathologies.

About this StructureAbout this Structure

1O0F is a Single protein structure of sequence from Bos taurus with as ligand. Active as Pancreatic ribonuclease, with EC number 3.1.27.5 Full crystallographic information is available from OCA.

ReferenceReference

High-resolution crystal structures of ribonuclease A complexed with adenylic and uridylic nucleotide inhibitors. Implications for structure-based design of ribonucleolytic inhibitors., Leonidas DD, Chavali GB, Oikonomakos NG, Chrysina ED, Kosmopoulou MN, Vlassi M, Frankling C, Acharya KR, Protein Sci. 2003 Nov;12(11):2559-74. PMID:14573867

Page seeded by OCA on Thu Feb 21 14:12:02 2008

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

OCA

@@ Line 1: / Line 1: @@
-[[Image:1o0f.gif|left|200px]]<br /><applet load="1o0f" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1o0f.gif|left|200px]]<br /><applet load="1o0f" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1o0f, resolution 1.50&Aring;" />
 '''RNASE A in complex with 3',5'-ADP'''<br />
 ==Overview==
-The crystal structures of bovine pancreatic ribonuclease A (RNase A) in, complex with 3',5'-ADP, 2',5'-ADP, 5'-ADP, U-2'-p and U-3'-p have been, determined at high resolution. The structures reveal that each inhibitor, binds differently in the RNase A active site by anchoring a phosphate, group in subsite P1. The most potent inhibitor of all five, 5'-ADP (Ki =, 1.2 microM), adopts a syn conformation (in contrast to 3',5'-ADP and, 2',5'-ADP, which adopt an anti), and it is the beta- rather than the, alpha-phosphate group that binds to P1. 3',5'-ADP binds with the, 5'-phosphate group in P1 and the adenosine in the B2 pocket. Two different, binding modes are observed in the two RNase A molecules of the asymmetric, unit for 2',5'-ADP. This inhibitor binds with either the 3' or the 5', phosphate groups in subsite P1, and in each case, the adenosine binds in, two different positions within the B2 subsite. The two uridilyl inhibitors, bind similarly with the uridine moiety in the B1 subsite but the placement, of a different phosphate group in P1 (2' versus 3') has significant, implications on their potency against RNase A. Comparative structural, analysis of the RNase A, eosinophil-derived neurotoxin (EDN), eosinophil, cationic protein (ECP), and human angiogenin (Ang) complexes with these, and other phosphonucleotide inhibitors provides a wealth of information, for structure-based design of inhibitors specific for each RNase. These, inhibitors could be developed to therapeutic agents that could control the, biological activities of EDN, ECP, and ANG, which play key roles in human, pathologies.
+The crystal structures of bovine pancreatic ribonuclease A (RNase A) in complex with 3',5'-ADP, 2',5'-ADP, 5'-ADP, U-2'-p and U-3'-p have been determined at high resolution. The structures reveal that each inhibitor binds differently in the RNase A active site by anchoring a phosphate group in subsite P1. The most potent inhibitor of all five, 5'-ADP (Ki = 1.2 microM), adopts a syn conformation (in contrast to 3',5'-ADP and 2',5'-ADP, which adopt an anti), and it is the beta- rather than the alpha-phosphate group that binds to P1. 3',5'-ADP binds with the 5'-phosphate group in P1 and the adenosine in the B2 pocket. Two different binding modes are observed in the two RNase A molecules of the asymmetric unit for 2',5'-ADP. This inhibitor binds with either the 3' or the 5' phosphate groups in subsite P1, and in each case, the adenosine binds in two different positions within the B2 subsite. The two uridilyl inhibitors bind similarly with the uridine moiety in the B1 subsite but the placement of a different phosphate group in P1 (2' versus 3') has significant implications on their potency against RNase A. Comparative structural analysis of the RNase A, eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP), and human angiogenin (Ang) complexes with these and other phosphonucleotide inhibitors provides a wealth of information for structure-based design of inhibitors specific for each RNase. These inhibitors could be developed to therapeutic agents that could control the biological activities of EDN, ECP, and ANG, which play key roles in human pathologies.
 ==About this Structure==
-O0F is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with A3P as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Pancreatic_ribonuclease Pancreatic ribonuclease], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.27.5 3.1.27.5] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1O0F OCA].
+O0F is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with <scene name='pdbligand=A3P:'>A3P</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Pancreatic_ribonuclease Pancreatic ribonuclease], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.27.5 3.1.27.5] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1O0F OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Pancreatic ribonuclease]]
 [[Category: Single protein]]
-[[Category: Chrysina, E.D.]]
+[[Category: Chrysina, E D.]]
-[[Category: Kosmopoulou, M.N.]]
+[[Category: Kosmopoulou, M N.]]
-[[Category: Leonidas, D.D.]]
+[[Category: Leonidas, D D.]]
-[[Category: Oikonomakos, N.G.]]
+[[Category: Oikonomakos, N G.]]
 [[Category: Vlassi, M.]]
 [[Category: A3P]]
@@ Line 23: / Line 23: @@
 [[Category: ribonuclease]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 22:42:24 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:12:02 2008''