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1afl

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[[Image:1afl.gif|left|200px]]<br /><applet load="1afl" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1afl, resolution 1.7&Aring;" />
 
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'''RIBONUCLEASE A IN COMPLEX WITH 5'-DIPHOSPHOADENOSINE 2'-PHOSPHATE AT 1.7 ANGSTROM RESOLUTION'''<br />
 
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==Overview==
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==RIBONUCLEASE A IN COMPLEX WITH 5'-DIPHOSPHOADENOSINE 2'-PHOSPHATE AT 1.7 ANGSTROM RESOLUTION==
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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.
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<StructureSection load='1afl' size='340' side='right'caption='[[1afl]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1afl]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AFL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1AFL FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATR:2-MONOPHOSPHOADENOSINE-5-DIPHOSPHATE'>ATR</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1afl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1afl OCA], [https://pdbe.org/1afl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1afl RCSB], [https://www.ebi.ac.uk/pdbsum/1afl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1afl ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/RNAS1_BOVIN RNAS1_BOVIN] Endonuclease that catalyzes the cleavage of RNA on the 3' side of pyrimidine nucleotides. Acts on single stranded and double stranded RNA.<ref>PMID:7479688</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/af/1afl_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1afl ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1AFL 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=ATR:'>ATR</scene> and <scene name='pdbligand=CIT:'>CIT</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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=1AFL OCA].
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*[[Ribonuclease 3D structures|Ribonuclease 3D structures]]
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== References ==
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==Reference==
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<references/>
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9154942 9154942]
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__TOC__
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</StructureSection>
[[Category: Bos taurus]]
[[Category: Bos taurus]]
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[[Category: Pancreatic ribonuclease]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Acharya KR]]
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[[Category: Acharya, K R.]]
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[[Category: Leonidas DD]]
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[[Category: Leonidas, D D.]]
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[[Category: ATR]]
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[[Category: CIT]]
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[[Category: endonuclease]]
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[[Category: hydrolase]]
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[[Category: nucleotide inhibitor]]
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[[Category: ribonuclease]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:43:58 2008''
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Current revision

RIBONUCLEASE A IN COMPLEX WITH 5'-DIPHOSPHOADENOSINE 2'-PHOSPHATE AT 1.7 ANGSTROM RESOLUTION

PDB ID 1afl

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