1tq9

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{{STRUCTURE_1tq9| PDB=1tq9 | SCENE= }}
{{STRUCTURE_1tq9| PDB=1tq9 | SCENE= }}
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'''Non-covalent swapped dimer of Bovine Seminal Ribonuclease in complex with 2'-DEOXYCYTIDINE-2'-DEOXYADENOSINE-3',5'-MONOPHOSPHATE'''
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===Non-covalent swapped dimer of Bovine Seminal Ribonuclease in complex with 2'-DEOXYCYTIDINE-2'-DEOXYADENOSINE-3',5'-MONOPHOSPHATE===
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==Overview==
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A growing number of pancreatic-type ribonucleases (RNases) present cytotoxic activity against malignant cells. The cytoxicity of these enzymes is related to their resistance to the ribonuclease protein inhibitor (RI). In particular, bovine seminal ribonuclease (BS-RNase) is toxic to tumor cells both in vitro and in vivo. BS-RNase is a covalent dimer with two intersubunit disulfide bridges between Cys(31) of one chain and Cys(32) of the second and vice versa. The native enzyme is an equilibrium mixture of two isomers, MxM and M=M. In the former the two subunits swap their N-terminal helices. The cytotoxic action is a peculiar property of MxM. In the reducing environment of cytosol, M=M dissociates into monomers, which are strongly inhibited by RI, whereas MxM remains as a non-covalent dimer (NCD), which evades RI. We have solved the crystal structure of NCD, carboxyamidomethylated at residues Cys(31) and Cys(32) (NCD-CAM), in a complex with 2'-deoxycitidylyl(3'-5')-2'-deoxyadenosine. The molecule reveals a quaternary structural organization much closer to MxM than to other N-terminal-swapped non-covalent dimeric forms of RNases. Model building of the complexes between these non-covalent dimers and RI reveals that NCD-CAM is the only dimer equipped with a quaternary organization capable of interfering seriously with the binding of the inhibitor. Moreover, a detailed comparative structural analysis of the dimers has highlighted the residues, which are mostly important in driving the quaternary structure toward that found in NCD-CAM.
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{{ABSTRACT_PUBMED_15192098}}
==About this Structure==
==About this Structure==
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==Reference==
==Reference==
Structure and stability of the non-covalent swapped dimer of bovine seminal ribonuclease: an enzyme tailored to evade ribonuclease protein inhibitor., Sica F, Di Fiore A, Merlino A, Mazzarella L, J Biol Chem. 2004 Aug 27;279(35):36753-60. Epub 2004 Jun 9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15192098 15192098]
Structure and stability of the non-covalent swapped dimer of bovine seminal ribonuclease: an enzyme tailored to evade ribonuclease protein inhibitor., Sica F, Di Fiore A, Merlino A, Mazzarella L, J Biol Chem. 2004 Aug 27;279(35):36753-60. Epub 2004 Jun 9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15192098 15192098]
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Population shift vs induced fit: the case of bovine seminal ribonuclease swapping dimer., Merlino A, Vitagliano L, Sica F, Zagari A, Mazzarella L, Biopolymers. 2004 Apr 15;73(6):689-95. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15048772 15048772]
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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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A potential allosteric subsite generated by domain swapping in bovine seminal ribonuclease., Vitagliano L, Adinolfi S, Sica F, Merlino A, Zagari A, Mazzarella L, J Mol Biol. 1999 Oct 29;293(3):569-77. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10543951 10543951]
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The unswapped chain of bovine seminal ribonuclease: Crystal structure of the free and liganded monomeric derivative., Sica F, Di Fiore A, Zagari A, Mazzarella L, Proteins. 2003 Aug 1;52(2):263-71. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12833549 12833549]
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Crystal structure of the dimeric unswapped form of bovine seminal ribonuclease., Berisio R, Sica F, De Lorenzo C, Di Fiore A, Piccoli R, Zagari A, Mazzarella L, FEBS Lett. 2003 Nov 6;554(1-2):105-10. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14596923 14596923]
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Swapping structural determinants of ribonucleases: an energetic analysis of the hinge peptide 16-22., Mazzarella K, Vitagliano L, Zagari A, Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):3799-803. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/7731986 7731986]
[[Category: Bos taurus]]
[[Category: Bos taurus]]
[[Category: Pancreatic ribonuclease]]
[[Category: Pancreatic ribonuclease]]
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[[Category: Cytotoxic action]]
[[Category: Cytotoxic action]]
[[Category: Protein-dinucleotide complex]]
[[Category: Protein-dinucleotide complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 10:14:54 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 21:19:32 2008''

Revision as of 18:19, 27 July 2008

Image:1tq9.png

Template:STRUCTURE 1tq9

Non-covalent swapped dimer of Bovine Seminal Ribonuclease in complex with 2'-DEOXYCYTIDINE-2'-DEOXYADENOSINE-3',5'-MONOPHOSPHATE

Template:ABSTRACT PUBMED 15192098

About this Structure

1TQ9 is a Single protein structure of sequence from Bos taurus. Full crystallographic information is available from OCA.

Reference

Structure and stability of the non-covalent swapped dimer of bovine seminal ribonuclease: an enzyme tailored to evade ribonuclease protein inhibitor., Sica F, Di Fiore A, Merlino A, Mazzarella L, J Biol Chem. 2004 Aug 27;279(35):36753-60. Epub 2004 Jun 9. PMID:15192098

Population shift vs induced fit: the case of bovine seminal ribonuclease swapping dimer., Merlino A, Vitagliano L, Sica F, Zagari A, Mazzarella L, Biopolymers. 2004 Apr 15;73(6):689-95. PMID:15048772

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

A potential allosteric subsite generated by domain swapping in bovine seminal ribonuclease., Vitagliano L, Adinolfi S, Sica F, Merlino A, Zagari A, Mazzarella L, J Mol Biol. 1999 Oct 29;293(3):569-77. PMID:10543951

The unswapped chain of bovine seminal ribonuclease: Crystal structure of the free and liganded monomeric derivative., Sica F, Di Fiore A, Zagari A, Mazzarella L, Proteins. 2003 Aug 1;52(2):263-71. PMID:12833549

Crystal structure of the dimeric unswapped form of bovine seminal ribonuclease., Berisio R, Sica F, De Lorenzo C, Di Fiore A, Piccoli R, Zagari A, Mazzarella L, FEBS Lett. 2003 Nov 6;554(1-2):105-10. PMID:14596923

Swapping structural determinants of ribonucleases: an energetic analysis of the hinge peptide 16-22., Mazzarella K, Vitagliano L, Zagari A, Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):3799-803. PMID:7731986

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