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[[Image:1jn4.gif|left|200px]]


{{Structure
==The Crystal Structure of Ribonuclease A in complex with 2'-deoxyuridine 3'-pyrophosphate (P'-5') adenosine==
|PDB= 1jn4 |SIZE=350|CAPTION= <scene name='initialview01'>1jn4</scene>, resolution 1.80&Aring;
<StructureSection load='1jn4' size='340' side='right'caption='[[1jn4]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND= <scene name='pdbligand=139:ADENOSINE-5&#39;-[TRIHYDROGEN DIPHOSPHATE] P&#39;-3&#39;-ESTER WITH 2&#39;-DEOXYURIDINE'>139</scene>
<table><tr><td colspan='2'>[[1jn4]] 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=1JN4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JN4 FirstGlance]. <br>
|ACTIVITY= [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]
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
|GENE=
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=139:ADENOSINE-5-[TRIHYDROGEN+DIPHOSPHATE]+P-3-ESTER+WITH+2-DEOXYURIDINE'>139</scene></td></tr>
}}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1jn4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jn4 OCA], [https://pdbe.org/1jn4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1jn4 RCSB], [https://www.ebi.ac.uk/pdbsum/1jn4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1jn4 ProSAT]</span></td></tr>
</table>
== Function ==
[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>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jn/1jn4_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=1jn4 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Recently, 3',5'-pyrophosphate-linked 2'-deoxyribodinucleotides were shown to be &gt;100-fold more effective inhibitors of RNase A superfamily enzymes than were the corresponding monophosphate-linked (i.e., standard) dinucleotides. Here, we have investigated two ribo analogues of these compounds, cytidine 3'-pyrophosphate (P'--&gt;5') adenosine (CppA) and uridine 3'-pyrophosphate (P'--&gt;5') adenosine (UppA), as potential substrates for RNase A and angiogenin. CppA and UppA are cleaved efficiently by RNase A, yielding as products 5'-AMP and cytidine or uridine cyclic 2',3'-phosphate. The k(cat)/K(m) values are only 4-fold smaller than for the standard dinucleotides CpA and UpA, and the K(m) values (10-16 microM) are lower than those reported for any earlier small substrates (e.g., 500-700 microM for CpA and UpA). The k(cat)/K(m) value for CppA with angiogenin is also only severalfold smaller than for CpA, but the effect of lengthening the internucleotide linkage on K(m) is more modest. Ribonucleotide 3',5'-pyrophosphate linkages were proposed previously to exist in nature as chemically labile intermediates in the pathway for the generation of cyclic 2',3'-phosphate termini in various RNAs. We demonstrate that in fact they are relatively stable (t(1/2) &gt; 15 days for uncatalyzed degradation of UppA at pH 6 and 25 degrees C) and that cleavage in vivo is most likely enzymatic. Replacements of the RNase A catalytic residues His12 and His119 by alanine reduce activity toward UppA by approximately 10(5)-and 10(3.3)-fold, respectively. Thus, both residues play important roles. His12 probably acts as a base catalyst in cleavage of UppA (as with RNA). However, the major function of His119 in RNA cleavage, protonation of the 5'-O leaving group, is not required for UppA cleavage because the pK(a) of the leaving group is much lower than that for RNA substrates. A crystal structure of the complex of RNase A with 2'-deoxyuridine 3'-pyrophosphate (P'--&gt;5') adenosine (dUppA), determined at 1.7 A resolution, together with models of the UppA complex based on this structure suggest that His119 contributes to UppA cleavage through a hydrogen bond with a nonbridging oxygen atom in the pyrophosphate and through pi-pi stacking with the six-membered ring of adenine.


'''The Crystal Structure of Ribonuclease A in complex with 2'-deoxyuridine 3'-pyrophosphate (P'-5') adenosine'''
Cleavage of 3',5'-pyrophosphate-linked dinucleotides by ribonuclease A and angiogenin.,Jardine AM, Leonidas DD, Jenkins JL, Park C, Raines RT, Acharya KR, Shapiro R Biochemistry. 2001 Aug 28;40(34):10262-72. PMID:11513604<ref>PMID:11513604</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1jn4" style="background-color:#fffaf0;"></div>


==Overview==
==See Also==
Recently, 3',5'-pyrophosphate-linked 2'-deoxyribodinucleotides were shown to be &gt;100-fold more effective inhibitors of RNase A superfamily enzymes than were the corresponding monophosphate-linked (i.e., standard) dinucleotides. Here, we have investigated two ribo analogues of these compounds, cytidine 3'-pyrophosphate (P'--&gt;5') adenosine (CppA) and uridine 3'-pyrophosphate (P'--&gt;5') adenosine (UppA), as potential substrates for RNase A and angiogenin. CppA and UppA are cleaved efficiently by RNase A, yielding as products 5'-AMP and cytidine or uridine cyclic 2',3'-phosphate. The k(cat)/K(m) values are only 4-fold smaller than for the standard dinucleotides CpA and UpA, and the K(m) values (10-16 microM) are lower than those reported for any earlier small substrates (e.g., 500-700 microM for CpA and UpA). The k(cat)/K(m) value for CppA with angiogenin is also only severalfold smaller than for CpA, but the effect of lengthening the internucleotide linkage on K(m) is more modest. Ribonucleotide 3',5'-pyrophosphate linkages were proposed previously to exist in nature as chemically labile intermediates in the pathway for the generation of cyclic 2',3'-phosphate termini in various RNAs. We demonstrate that in fact they are relatively stable (t(1/2) &gt; 15 days for uncatalyzed degradation of UppA at pH 6 and 25 degrees C) and that cleavage in vivo is most likely enzymatic. Replacements of the RNase A catalytic residues His12 and His119 by alanine reduce activity toward UppA by approximately 10(5)-and 10(3.3)-fold, respectively. Thus, both residues play important roles. His12 probably acts as a base catalyst in cleavage of UppA (as with RNA). However, the major function of His119 in RNA cleavage, protonation of the 5'-O leaving group, is not required for UppA cleavage because the pK(a) of the leaving group is much lower than that for RNA substrates. A crystal structure of the complex of RNase A with 2'-deoxyuridine 3'-pyrophosphate (P'--&gt;5') adenosine (dUppA), determined at 1.7 A resolution, together with models of the UppA complex based on this structure suggest that His119 contributes to UppA cleavage through a hydrogen bond with a nonbridging oxygen atom in the pyrophosphate and through pi-pi stacking with the six-membered ring of adenine.
*[[Ribonuclease 3D structures|Ribonuclease 3D structures]]
 
== References ==
==About this Structure==
<references/>
1JN4 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JN4 OCA].
__TOC__
 
</StructureSection>
==Reference==
Cleavage of 3',5'-pyrophosphate-linked dinucleotides by ribonuclease A and angiogenin., Jardine AM, Leonidas DD, Jenkins JL, Park C, Raines RT, Acharya KR, Shapiro R, Biochemistry. 2001 Aug 28;40(34):10262-72. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11513604 11513604]
[[Category: Bos taurus]]
[[Category: Bos taurus]]
[[Category: Pancreatic ribonuclease]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Acharya KR]]
[[Category: Acharya, K R.]]
[[Category: Jardine AM]]
[[Category: Jardine, A M.]]
[[Category: Jenkins JL]]
[[Category: Jenkins, J L.]]
[[Category: Leonidas DD]]
[[Category: Leonidas, D D.]]
[[Category: Park C]]
[[Category: Park, C.]]
[[Category: Raines RT]]
[[Category: Raines, R T.]]
[[Category: Shapiro R]]
[[Category: Shapiro, R.]]
[[Category: 139]]
[[Category: endonuclease]]
[[Category: hydrolase]]
[[Category: nucleotide inhibitor]]
[[Category: ribonuclease]]
 
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