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1un5

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ARH-II, AN ANGIOGENIN/RNASE A CHIMERA

Structural highlights

1un5 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.6Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

ANGI_HUMAN Defects in ANG are the cause of susceptibility to amyotrophic lateral sclerosis type 9 (ALS9) [MIM: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.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Function

RNAS1_BOVIN Endonuclease that catalyzes the cleavage of RNA on the 3' side of pyrimidine nucleotides. Acts on single stranded and double stranded RNA.^[7] 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.^[8] ^[9]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

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^[10]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wu D, Yu W, Kishikawa H, Folkerth RD, Iafrate AJ, Shen Y, Xin W, Sims K, Hu GF. Angiogenin loss-of-function mutations in amyotrophic lateral sclerosis. Ann Neurol. 2007 Dec;62(6):609-17. PMID:17886298 doi:10.1002/ana.21221
↑ Greenway MJ, Alexander MD, Ennis S, Traynor BJ, Corr B, Frost E, Green A, Hardiman O. A novel candidate region for ALS on chromosome 14q11.2. Neurology. 2004 Nov 23;63(10):1936-8. PMID:15557516
↑ Greenway MJ, Andersen PM, Russ C, Ennis S, Cashman S, Donaghy C, Patterson V, Swingler R, Kieran D, Prehn J, Morrison KE, Green A, Acharya KR, Brown RH Jr, Hardiman O. ANG mutations segregate with familial and 'sporadic' amyotrophic lateral sclerosis. Nat Genet. 2006 Apr;38(4):411-3. Epub 2006 Feb 26. PMID:16501576 doi:10.1038/ng1742
↑ Crabtree B, Thiyagarajan N, Prior SH, Wilson P, Iyer S, Ferns T, Shapiro R, Brew K, Subramanian V, Acharya KR. Characterization of human angiogenin variants implicated in amyotrophic lateral sclerosis. Biochemistry. 2007 Oct 23;46(42):11810-8. Epub 2007 Sep 27. PMID:17900154 doi:10.1021/bi701333h
↑ Gellera C, Colombrita C, Ticozzi N, Castellotti B, Bragato C, Ratti A, Taroni F, Silani V. Identification of new ANG gene mutations in a large cohort of Italian patients with amyotrophic lateral sclerosis. Neurogenetics. 2008 Feb;9(1):33-40. Epub 2007 Dec 18. PMID:18087731 doi:10.1007/s10048-007-0111-3
↑ Conforti FL, Sprovieri T, Mazzei R, Ungaro C, La Bella V, Tessitore A, Patitucci A, Magariello A, Gabriele AL, Tedeschi G, Simone IL, Majorana G, Valentino P, Condino F, Bono F, Monsurro MR, Muglia M, Quattrone A. A novel Angiogenin gene mutation in a sporadic patient with amyotrophic lateral sclerosis from southern Italy. Neuromuscul Disord. 2008 Jan;18(1):68-70. Epub 2007 Aug 20. PMID:17703939 doi:S0960-8966(07)00676-1
↑ delCardayre SB, Ribo M, Yokel EM, Quirk DJ, Rutter WJ, Raines RT. Engineering ribonuclease A: production, purification and characterization of wild-type enzyme and mutants at Gln11. Protein Eng. 1995 Mar;8(3):261-73. PMID:7479688
↑ Saxena SK, Rybak SM, Davey RT Jr, Youle RJ, Ackerman EJ. Angiogenin is a cytotoxic, tRNA-specific ribonuclease in the RNase A superfamily. J Biol Chem. 1992 Oct 25;267(30):21982-6. PMID:1400510
↑ Dickson KA, Kang DK, Kwon YS, Kim JC, Leland PA, Kim BM, Chang SI, Raines RT. Ribonuclease inhibitor regulates neovascularization by human angiogenin. Biochemistry. 2009 May 12;48(18):3804-6. doi: 10.1021/bi9005094. PMID:19354288 doi:10.1021/bi9005094
↑ Holloway DE, Chavali GB, Hares MC, Baker MD, Subbarao GV, Shapiro R, Acharya KR. Crystallographic studies on structural features that determine the enzymatic specificity and potency of human angiogenin: Thr44, Thr80, and residues 38-41. Biochemistry. 2004 Feb 10;43(5):1230-41. PMID:14756559 doi:10.1021/bi035654+

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1un5"

Categories: Homo sapiens | Large Structures | Acharya KR | Baker MD | Holloway DE

@@ Line 1: / Line 1: @@
 ==ARH-II, AN ANGIOGENIN/RNASE A CHIMERA==
-<StructureSection load='1un5' size='340' side='right' caption='[[1un5]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
+<StructureSection load='1un5' size='340' side='right'caption='[[1un5]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1un5]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UN5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1UN5 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1un5]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UN5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UN5 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[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]], [[1un4|1un4]], [[2ang|2ang]]</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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </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=1un5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1un5 OCA], [https://pdbe.org/1un5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1un5 RCSB], [https://www.ebi.ac.uk/pdbsum/1un5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1un5 ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1un5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1un5 OCA], [http://pdbe.org/1un5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1un5 RCSB], [http://www.ebi.ac.uk/pdbsum/1un5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1un5 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/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> [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]]
@@ Line 30: / Line 33: @@
 ==See Also==
-*[[Ribonuclease|Ribonuclease]]
+*[[Ribonuclease 3D structures|Ribonuclease 3D structures]]
-*[[Temp|Temp]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Pancreatic ribonuclease]]
+[[Category: Large Structures]]
-[[Category: Acharya, K R]]
+[[Category: Acharya KR]]
-[[Category: Baker, M D]]
+[[Category: Baker MD]]
-[[Category: Holloway, D E]]
+[[Category: Holloway DE]]
-[[Category: Angiogenesis]]
-[[Category: Angiogenin]]
-[[Category: Chimera]]
-[[Category: Homolog scanning mutagenesis]]
-[[Category: Hybrid]]
-[[Category: Hydrolase]]

1un5

From Proteopedia

Current revision

ARH-II, AN ANGIOGENIN/RNASE A CHIMERA

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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