Ribonuclease inhibitor

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<table width='550' align='right' cellpadding='5'><tr><td rowspan='2'>&nbsp;</td><td bgcolor='#eeeeee'>{{STRUCTURE_1z7x| PDB=1z7x | SIZE=540| SCENE=Ribonuclease_inhibitor/1z7x/2 }} </td></tr><tr><td bgcolor='#eeeeee'><center>
<table width='550' align='right' cellpadding='5'><tr><td rowspan='2'>&nbsp;</td><td bgcolor='#eeeeee'>{{STRUCTURE_1z7x| PDB=1z7x | SIZE=540| SCENE=Ribonuclease_inhibitor/1z7x/2 }} </td></tr><tr><td bgcolor='#eeeeee'><center>
·· {{Link Toggle BlackWhiteBackground}} ··<br> {{Link Toggle Ribonuclease_inhibitor/Chain_x}} ·· {{Link Toggle Ribonuclease_inhibitor/Chain_y}} <br> {{Link Toggle Ribonuclease_inhibitor/Chain_w}} ·· {{Link Toggle Ribonuclease_inhibitor/Chain_z}}<br></center></td></tr></table>
·· {{Link Toggle BlackWhiteBackground}} ··<br> {{Link Toggle Ribonuclease_inhibitor/Chain_x}} ·· {{Link Toggle Ribonuclease_inhibitor/Chain_y}} <br> {{Link Toggle Ribonuclease_inhibitor/Chain_w}} ·· {{Link Toggle Ribonuclease_inhibitor/Chain_z}}<br></center></td></tr></table>
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'''Ribonuclease inhibitors (RI)''' are a family of large (~450 residues, ~49 kDa), acidic (pI ~4.7), proteins that catalyze the degradation of [http://en.wikipedia.org/wiki/Ribonuclease ribonucleases]. Human RI(hRI) is a major cellular protein, comprising ~0.1% of all cellular protein by weight. <ref>PMID: 11582809</ref> Human RI ([[1z7x]]) is shown to the right complexed as a dimer with RNase 1.
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and plays an important role in regulating the lifetime of [http://en.wikipedia.org/wiki/RNA RNA].
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Human ribonuclease inhibitor (hRI) is a protein that binds to and inhibits ribonucleases. Ribonucleases(RNase) are a family of enzymes that degrade RNA. RNases are often cytotoxic which gives them unique cancer fighting properties. However, when bound to an RI they no longer display catalytic ability.
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Ribonucleases are enzymes that degrade RNA and are often [http://en.wikipedia.org/wiki/Cytotoxicity cytotoxic] which gives them chemotherapeutic properties. However, when bound to an RI they are no longer functional. Understanding the mechanism through which RI identifies and binds to RNases will allow scientists to design/modify RNases to evade hRI. In fact, one drug, Onconase (ONC), a ribonuclease from the Northern Leopard Frog ([http://en.wikipedia.org/wiki/Northern_Leopard_Frog Rana pipiens]), is now in Phase III clinical trials as a cancer chemotherapeutic agent <ref>PMID:20173221</ref>.
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<scene name='Ribonuclease_inhibitor/Arg91/5'>Arg 91</scene>
<scene name='Ribonuclease_inhibitor/Arg91/5'>Arg 91</scene>
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==References==
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<references />

Revision as of 07:22, 8 November 2011

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Ribonuclease inhibitors (RI) are a family of large (~450 residues, ~49 kDa), acidic (pI ~4.7), proteins that catalyze the degradation of ribonucleases. Human RI(hRI) is a major cellular protein, comprising ~0.1% of all cellular protein by weight. [1] Human RI (1z7x) is shown to the right complexed as a dimer with RNase 1.

and plays an important role in regulating the lifetime of RNA.

Ribonucleases are enzymes that degrade RNA and are often cytotoxic which gives them chemotherapeutic properties. However, when bound to an RI they are no longer functional. Understanding the mechanism through which RI identifies and binds to RNases will allow scientists to design/modify RNases to evade hRI. In fact, one drug, Onconase (ONC), a ribonuclease from the Northern Leopard Frog (Rana pipiens), is now in Phase III clinical trials as a cancer chemotherapeutic agent [2].



Interactions between hRI and RNase 1 [3]

References

  1. Shapiro R. Cytoplasmic ribonuclease inhibitor. Methods Enzymol. 2001;341:611-28. PMID:11582809
  2. Zwolinska M, Smolewski P. [Onconase: a ribonuclease with antitumor activity]. Postepy Hig Med Dosw (Online). 2010 Feb 19;64:58-66. PMID:20173221
  3. . PMID:173506502

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Abe Weintraub, Michal Harel, Alexander Berchansky, Joel L. Sussman

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