1yv6

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[[Image:1yv6.gif|left|200px]]
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{{STRUCTURE_1yv6| PDB=1yv6 | SCENE= }}
{{STRUCTURE_1yv6| PDB=1yv6 | SCENE= }}
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'''X-ray structure of M23L onconase at 298K'''
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===X-ray structure of M23L onconase at 298K===
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==Overview==
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Onconase (ONC), a member of the RNase A superfamily extracted from oocytes of Rana pipiens, is an effective cancer killer. It is currently used in treatment of various forms of cancer. ONC antitumor properties depend on its ribonucleolytic activity that is low in comparison with other members of the superfamily. The most damaging side effect from Onconase treatment is renal toxicity, which seems to be caused by the unusual stability of the enzyme. Therefore, mutants with reduced thermal stability and/or increased catalytic activity may have significant implications for human cancer chemotherapy. In this context, we have determined the crystal structures of two Onconase mutants (M23L-ONC and C87S,des103-104-ONC) and performed molecular dynamic simulations of ONC and C87S,des103-104-ONC with the aim of explaining on structural grounds the modifications of the activity and thermal stability of the mutants. The results also provide the molecular bases to explain the lower catalytic activity of Onconase compared with RNase A and the unusually high thermal stability of the amphibian enzyme.
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The line below this paragraph, {{ABSTRACT_PUBMED_15728177}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 15728177 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15728177}}
==About this Structure==
==About this Structure==
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==Reference==
==Reference==
The importance of dynamic effects on the enzyme activity: X-ray structure and molecular dynamics of onconase mutants., Merlino A, Mazzarella L, Carannante A, Di Fiore A, Di Donato A, Notomista E, Sica F, J Biol Chem. 2005 May 6;280(18):17953-60. Epub 2005 Feb 22. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15728177 15728177]
The importance of dynamic effects on the enzyme activity: X-ray structure and molecular dynamics of onconase mutants., Merlino A, Mazzarella L, Carannante A, Di Fiore A, Di Donato A, Notomista E, Sica F, J Biol Chem. 2005 May 6;280(18):17953-60. Epub 2005 Feb 22. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15728177 15728177]
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Reversible substrate-induced domain motions in ribonuclease A., Vitagliano L, Merlino A, Zagari A, Mazzarella L, Proteins. 2002 Jan 1;46(1):97-104. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11746706 11746706]
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Productive and nonproductive binding to ribonuclease A: X-ray structure of two complexes with uridylyl(2',5')guanosine., Vitagliano L, Merlino A, Zagari A, Mazzarella L, Protein Sci. 2000 Jun;9(6):1217-25. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10892814 10892814]
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Binding of a substrate analog to a domain swapping protein: X-ray structure of the complex of bovine seminal ribonuclease with uridylyl(2',5')adenosine., Vitagliano L, Adinolfi S, Riccio A, Sica F, Zagari A, Mazzarella L, Protein Sci. 1998 Aug;7(8):1691-9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10082366 10082366]
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Atomic resolution structures of ribonuclease A at six pH values., Berisio R, Sica F, Lamzin VS, Wilson KS, Zagari A, Mazzarella L, Acta Crystallogr D Biol Crystallogr. 2002 Mar;58(Pt 3):441-50. Epub 2002, Feb 21. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11856829 11856829]
[[Category: Rana pipiens]]
[[Category: Rana pipiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: Ribonuclease]]
[[Category: Ribonuclease]]
[[Category: Small conformational change]]
[[Category: Small conformational change]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 16:49:42 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 23:52:46 2008''

Revision as of 20:52, 27 July 2008

Image:1yv6.png

Template:STRUCTURE 1yv6

X-ray structure of M23L onconase at 298K

Template:ABSTRACT PUBMED 15728177

About this Structure

1YV6 is a Single protein structure of sequence from Rana pipiens. Full crystallographic information is available from OCA.

Reference

The importance of dynamic effects on the enzyme activity: X-ray structure and molecular dynamics of onconase mutants., Merlino A, Mazzarella L, Carannante A, Di Fiore A, Di Donato A, Notomista E, Sica F, J Biol Chem. 2005 May 6;280(18):17953-60. Epub 2005 Feb 22. PMID:15728177

Reversible substrate-induced domain motions in ribonuclease A., Vitagliano L, Merlino A, Zagari A, Mazzarella L, Proteins. 2002 Jan 1;46(1):97-104. PMID:11746706

Productive and nonproductive binding to ribonuclease A: X-ray structure of two complexes with uridylyl(2',5')guanosine., Vitagliano L, Merlino A, Zagari A, Mazzarella L, Protein Sci. 2000 Jun;9(6):1217-25. PMID:10892814

Binding of a substrate analog to a domain swapping protein: X-ray structure of the complex of bovine seminal ribonuclease with uridylyl(2',5')adenosine., Vitagliano L, Adinolfi S, Riccio A, Sica F, Zagari A, Mazzarella L, Protein Sci. 1998 Aug;7(8):1691-9. PMID:10082366

Atomic resolution structures of ribonuclease A at six pH values., Berisio R, Sica F, Lamzin VS, Wilson KS, Zagari A, Mazzarella L, Acta Crystallogr D Biol Crystallogr. 2002 Mar;58(Pt 3):441-50. Epub 2002, Feb 21. PMID:11856829

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