1gv7: Difference between revisions
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==Overview== | ==Overview== | ||
Angiogenin and ribonuclease A share 33% sequence identity but have | Angiogenin and ribonuclease A share 33% sequence identity but have distinct functions. Angiogenin is a potent inducer of angiogenesis that is only weakly ribonucleolytic, whereas ribonuclease A is a robust ribonuclease that is not angiogenic. A chimera ("ARH-I"), in which angiogenin residues 58-70 are replaced with residues 59-73 of ribonuclease A, has intermediate ribonucleolytic potency and no angiogenic activity. Here we report a crystal structure of ARH-I that reveals the molecular basis for these characteristics. The ribonuclease A-derived (guest) segment adopts a structure largely similar to that in ribonuclease A, and successfully converts this region from a cell-binding site to a purine-binding site. At the same time, its presence causes complex changes in the angiogenin-derived (host) portion that account for much of the increased ribonuclease activity of ARH-I. Guest-host interactions of this type probably occur more generally in protein chimeras, emphasizing the importance of direct structural information for understanding the functional behavior of such molecules. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Pancreatic ribonuclease]] | [[Category: Pancreatic ribonuclease]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Acharya, K | [[Category: Acharya, K R.]] | ||
[[Category: Hares, M | [[Category: Hares, M C.]] | ||
[[Category: Holloway, D | [[Category: Holloway, D E.]] | ||
[[Category: Leonidas, D | [[Category: Leonidas, D D.]] | ||
[[Category: Shapiro, R.]] | [[Category: Shapiro, R.]] | ||
[[Category: CIT]] | [[Category: CIT]] | ||
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[[Category: pancreatic ribonuclease]] | [[Category: pancreatic ribonuclease]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:54:25 2008'' | ||
Revision as of 13:54, 21 February 2008
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ARH-I, AN ANGIOGENIN/RNASE A CHIMERA
OverviewOverview
Angiogenin and ribonuclease A share 33% sequence identity but have distinct functions. Angiogenin is a potent inducer of angiogenesis that is only weakly ribonucleolytic, whereas ribonuclease A is a robust ribonuclease that is not angiogenic. A chimera ("ARH-I"), in which angiogenin residues 58-70 are replaced with residues 59-73 of ribonuclease A, has intermediate ribonucleolytic potency and no angiogenic activity. Here we report a crystal structure of ARH-I that reveals the molecular basis for these characteristics. The ribonuclease A-derived (guest) segment adopts a structure largely similar to that in ribonuclease A, and successfully converts this region from a cell-binding site to a purine-binding site. At the same time, its presence causes complex changes in the angiogenin-derived (host) portion that account for much of the increased ribonuclease activity of ARH-I. Guest-host interactions of this type probably occur more generally in protein chimeras, emphasizing the importance of direct structural information for understanding the functional behavior of such molecules.
About this StructureAbout this Structure
1GV7 is a Single protein structure of sequence from Homo sapiens, bos taurus with as ligand. Active as Pancreatic ribonuclease, with EC number 3.1.27.5 Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
Guest-host crosstalk in an angiogenin-RNase A chimeric protein., Holloway DE, Shapiro R, Hares MC, Leonidas DD, Acharya KR, Biochemistry. 2002 Aug 20;41(33):10482-9. PMID:12173935
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