1h0d: Difference between revisions

Revision as of 08:34, 26 June 2019

Crystal structure of Human Angiogenin in complex with Fab fragment of its monoclonal antibody mAb 26-2F

Structural highlights

1h0d is a 3 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	GOL, SO4
NonStd Res:	PCA
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

[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.^[7] ^[8]

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

The murine monoclonal antibody 26-2F neutralizes the angiogenic and ribonucleolytic activities of human angiogenin (ANG) and is highly effective in preventing the establishment and metastatic dissemination of human tumors in athymic mice. Here we report a 2.0 A resolution crystal structure for the complex of ANG with the Fab fragment of 26-2F that reveals the detailed interactions between ANG and the complementarity-determining regions (CDRs) of the antibody. Surprisingly, Fab binding induces a dramatic conformational change in the cell binding region of ANG at the opposite end of the molecule from the combining site; crosslinking experiments indicate that this rearrangement also occurs in solution. The ANG-Fab complex structure should be invaluable for designing maximally humanized versions of 26-2F for potential clinical use.

The crystal structure of human angiogenin in complex with an antitumor neutralizing antibody.,Chavali GB, Papageorgiou AC, Olson KA, Fett JW, Hu G, Shapiro R, Acharya KR Structure. 2003 Jul;11(7):875-85. PMID:12842050^[9]

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
↑ 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
↑ Chavali GB, Papageorgiou AC, Olson KA, Fett JW, Hu G, Shapiro R, Acharya KR. The crystal structure of human angiogenin in complex with an antitumor neutralizing antibody. Structure. 2003 Jul;11(7):875-85. PMID:12842050

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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

[2] 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

[3] 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

[4] 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

[5] 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

[6] 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

[7] 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

[8] 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

[9] Chavali GB, Papageorgiou AC, Olson KA, Fett JW, Hu G, Shapiro R, Acharya KR. The crystal structure of human angiogenin in complex with an antitumor neutralizing antibody. Structure. 2003 Jul;11(7):875-85. PMID:12842050

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@@ Line 1: / Line 1: @@
 ==Crystal structure of Human Angiogenin in complex with Fab fragment of its monoclonal antibody mAb 26-2F==
-<StructureSection load='1h0d' size='340' side='right' caption='[[1h0d]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+<StructureSection load='1h0d' size='340' side='right'caption='[[1h0d]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1h0d]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H0D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1H0D FirstGlance]. <br>
@@ Line 16: / Line 16: @@
 Check<jmol>
    <jmolCheckbox>
-     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h0/1h0d_consurf.spt"</scriptWhenChecked>
+     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h0/1h0d_consurf.spt"</scriptWhenChecked>
      <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
      <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 33: / Line 33: @@
 ==See Also==
+*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
 *[[Ribonuclease|Ribonuclease]]
 *[[Temp|Temp]]
-*[[3D structures of monoclonal antibody|3D structures of monoclonal antibody]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Acharya, K R]]
 [[Category: Chavali, G B]]

1h0d: Difference between revisions

Revision as of 08:34, 26 June 2019

Crystal structure of Human Angiogenin in complex with Fab fragment of its monoclonal antibody mAb 26-2F

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

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Proteopedia Page Contributors and Editors (what is this?)

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