1afk: Difference between revisions
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[[Image:1afk.gif|left|200px]]<br /> | [[Image:1afk.gif|left|200px]]<br /><applet load="1afk" size="450" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="1afk" size="450" color="white" frame="true" align="right" spinBox="true" | |||
caption="1afk, resolution 1.7Å" /> | caption="1afk, resolution 1.7Å" /> | ||
'''CRYSTAL STRUCTURE OF RIBONUCLEASE A IN COMPLEX WITH 5'-DIPHOSPHOADENOSINE-3'-PHOSPHATE'''<br /> | '''CRYSTAL STRUCTURE OF RIBONUCLEASE A IN COMPLEX WITH 5'-DIPHOSPHOADENOSINE-3'-PHOSPHATE'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
1AFK 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 PAP 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] | 1AFK 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 PAP 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] Known structural/functional Sites: <scene name='pdbsite=CA1:Ppa3'-P Binds To The Cat Site'>CA1</scene> and <scene name='pdbsite=CAT:Ppa3'-P Binds To The Cat Site'>CAT</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1AFK OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: ribonuclease]] | [[Category: ribonuclease]] | ||
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Revision as of 15:04, 18 December 2007
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CRYSTAL STRUCTURE OF RIBONUCLEASE A IN COMPLEX WITH 5'-DIPHOSPHOADENOSINE-3'-PHOSPHATE
OverviewOverview
High-resolution (1.7 A) crystal structures have been determined for bovine, pancreatic ribonuclease A (RNase A) complexed with 5'-diphosphoadenosine, 3'-phosphate (ppA-3'-p) and 5'-diphosphoadenosine 2'-phosphate (ppA-2'-p), as well as for a native structure refined to 2.0 A. These nucleotide, phosphates are the two most potent inhibitors of RNase A reported so far, with Ki values of 240 and 520 nM, respectively. The binding modes and, conformations of ppA-3'-p and ppA-2'-p were found to differ markedly from, those anticipated on the basis of earlier structures of RNase A complexes., The key difference is that the 5'-beta-phosphate rather than the, 5'-alpha-phosphate of each inhibitor occupies the P1 phosphate binding, site. As a consequence, the ribose moieties of the two nucleotides are, shifted by approximately 2 A compared to the positions of their, counterparts in earlier complexes, and the adenine rings are rotated into, unusual syn conformations. Thus, the six-membered and five-membered rings, of both adenines are reversed with respect to the others but nonetheless, engage in extensive interactions with the residues that form the B2 purine, binding site of RNase A. Despite the close structural similarity of the, two inhibitors, the puckers of their furanose rings are different:, C2'-endo and C3'-endo, respectively. Moreover, their 5'-alpha-phosphates, and 3'(2')-monophosphates interact with largely different sets of RNase, residues. The results of this crystallographic study emphasize the, difficulties inherent in qualitative modeling of protein-inhibitor, interactions and the compelling reasons for high-resolution structural, studies in which quantitative design of improved inhibitors was enabled., The structures presented here provide a promising starting point for the, rational design of tight-binding RNase inhibitors, which may be used as, therapeutic agents in restraining the ribonucleolytic activities of RNase, homologues such as angiogenin, eosinophil-derived neurotoxin, and, eosinophil cationic protein.
About this StructureAbout this Structure
1AFK is a Single protein structure of sequence from Bos taurus with PAP as ligand. Active as Pancreatic ribonuclease, with EC number 3.1.27.5 Known structural/functional Sites: and . Full crystallographic information is available from OCA.
ReferenceReference
Crystal structures of ribonuclease A complexes with 5'-diphosphoadenosine 3'-phosphate and 5'-diphosphoadenosine 2'-phosphate at 1.7 A resolution., Leonidas DD, Shapiro R, Irons LI, Russo N, Acharya KR, Biochemistry. 1997 May 6;36(18):5578-88. PMID:9154942
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