View source for 1un4


==CRYSTAL STRUCTURE OF HUMAN ANGIOGENIN VARIANT T80A==
<StructureSection load='1un4' size='340' side='right'caption='[[1un4]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1un4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1h0e 1h0e]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UN4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UN4 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1a4y|1a4y]], [[1ang|1ang]], [[1awz|1awz]], [[1b1e|1b1e]], [[1b1i|1b1i]], [[1b1j|1b1j]], [[1gv7|1gv7]], [[1h0d|1h0d]], [[1h52|1h52]], [[1h53|1h53]], [[1hby|1hby]], [[1k58|1k58]], [[1k59|1k59]], [[1k5a|1k5a]], [[1k5b|1k5b]], [[1un3|1un3]], [[1un5|1un5]], [[2ang|2ang]]</div></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Pancreatic_ribonuclease Pancreatic ribonuclease], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.27.5 3.1.27.5] </span></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=1un4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1un4 OCA], [https://pdbe.org/1un4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1un4 RCSB], [https://www.ebi.ac.uk/pdbsum/1un4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1un4 ProSAT]</span></td></tr>
</table>
== Disease ==
[[https://www.uniprot.org/uniprot/ANGI_HUMAN ANGI_HUMAN]] Defects in ANG are the cause of susceptibility to amyotrophic lateral sclerosis type 9 (ALS9) [MIM:[https://omim.org/entry/611895 611895]]. ALS is a degenerative disorder of motor neurons in the cortex, brain stem and spinal cord. ALS is characterized by muscular weakness and atrophy.<ref>PMID:17886298</ref> <ref>PMID:15557516</ref> <ref>PMID:16501576</ref> <ref>PMID:17900154</ref> <ref>PMID:18087731</ref> <ref>PMID:17703939</ref>  
== Function ==
[[https://www.uniprot.org/uniprot/ANGI_HUMAN ANGI_HUMAN]] May function as a tRNA-specific ribonuclease that abolishes protein synthesis by specifically hydrolyzing cellular tRNAs. Binds to actin on the surface of endothelial cells; once bound, angiogenin is endocytosed and translocated to the nucleus. Angiogenin induces vascularization of normal and malignant tissues. Angiogenic activity is regulated by interaction with RNH1 in vivo.<ref>PMID:1400510</ref> <ref>PMID:19354288</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/un/1un4_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=1un4 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human angiogenin (Ang) is a potent inducer of blood vessel formation and is a member of the pancreatic ribonuclease superfamily. Its enzymatic activity is unusually weak and biased toward cleavage after cytidine nucleotides. As part of an ongoing investigation into the structural basis of Ang's characteristic activity, we have determined the crystal structures of three Ang variants having novel activity. (i) The structure of T44D-Ang indicates that Asp44 can participate directly in pyrimidine binding and that the intrinsic hydrogen-bonding capability of this residue largely governs the pyrimidine specificity of this variant. Unexpectedly, the mutation also causes the most extensive disruption of the C-terminus seen in any Ang variant thus far. This allows the side chain of Arg101 to penetrate the B(1) site, raising the possibility that it participates in substrate binding as occurs in ribonuclease 4. (ii) The structure of T80A-Ang supports the view that Thr80 plays little role in maintaining the obstructive conformation of the C-terminus and that its participation in a hydrogen bond with Thr44 selectively weakens the interaction between Thr44 and N3 of cytosine. (iii) ARH-II is an angiogenin/RNase A chimera in which residues 38-41 of Ang are replaced with the corresponding residues (38-42) of RNase A. Its structure suggests that the guest segment influences catalysis by subtle means, possibly by reducing the pK(a) of the catalytic lysine. The loss of angiogenic activity is not attributable to disruption of known cell-binding or nuclear translocation sites but may be a consequence of the chimera's enhanced ribonucleolytic activity.

Crystallographic studies on structural features that determine the enzymatic specificity and potency of human angiogenin: Thr44, Thr80, and residues 38-41.,Holloway DE, Chavali GB, Hares MC, Baker MD, Subbarao GV, Shapiro R, Acharya KR Biochemistry. 2004 Feb 10;43(5):1230-41. PMID:14756559<ref>PMID:14756559</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1un4" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ribonuclease 3D structures|Ribonuclease 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Pancreatic ribonuclease]]
[[Category: Acharya, K R]]
[[Category: Chavali, G B]]
[[Category: Holloway, D E]]
[[Category: Angiogenesis]]
[[Category: Endonuclease]]
[[Category: Hydrolase]]
[[Category: Nuclease]]
[[Category: Pyrrolidone carboxylic acid]]
[[Category: Ribonuclease]]