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3bcm

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{{STRUCTURE_3bcm| PDB=3bcm | SCENE= }}
{{STRUCTURE_3bcm| PDB=3bcm | SCENE= }}
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'''Crystal Structure of The Unswapped Form of P19A/L28Q/N67D BS-RNase'''
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===Crystal Structure of The Unswapped Form of P19A/L28Q/N67D BS-RNase===
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==Overview==
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Bovine seminal ribonuclease exists in the native state as an equilibrium mixture of a swapped and an unswapped dimer. The molecular envelope and the exposed surface of the two isomers are practically indistinguishable and their diversity is almost completely buried in the interior of the protein. Surprisingly, the cytotoxic and antitumor activity of the enzyme is a peculiar property of the swapped dimer. This buried diversity comes into light in the reducing environment of the cytosol, where the unswapped dimer dissociates into monomers, whereas the swapped one generates a metastable dimeric form (NCD-BS) with a quaternary assembly that allows the molecule to escape the protein inhibitor of ribonucleases. The stability of this quaternary shape was mainly attributed to the combined presence of Pro19 and Leu28. We have prepared and fully characterized by X-ray diffraction the double mutant P19A/L28Q (PALQ) of the seminal enzyme. While the swapped and unswapped forms of the mutant have structures very similar to that of the corresponding wild-type forms, the non-covalent form (NCD-PALQ) adopts an opened quaternary structure, different from that of NCD-BS. Moreover, model building clearly indicates that NCD-PALQ can be easily sequestered by the protein inhibitor. In agreement with these results, cytotoxic assays have revealed that PALQ has limited activity, whereas the single mutants P19A and L28Q display cytotoxic activity against malignant cells almost as large as the wild-type enzyme. The significant increase in the antitumor activity, brought about by the substitution of just two residues in going from the double mutant to the wild-type enzyme, suggests a new strategy to improve this important biological property by strengthening the interface that stabilizes the quaternary structure of NCD-BS.
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{{ABSTRACT_PUBMED_18164315}}
==About this Structure==
==About this Structure==
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==Reference==
==Reference==
The buried diversity of bovine seminal ribonuclease: shape and cytotoxicity of the swapped non-covalent form of the enzyme., Merlino A, Ercole C, Picone D, Pizzo E, Mazzarella L, Sica F, J Mol Biol. 2008 Feb 15;376(2):427-37. Epub 2007 Nov 12. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18164315 18164315]
The buried diversity of bovine seminal ribonuclease: shape and cytotoxicity of the swapped non-covalent form of the enzyme., Merlino A, Ercole C, Picone D, Pizzo E, Mazzarella L, Sica F, J Mol Biol. 2008 Feb 15;376(2):427-37. Epub 2007 Nov 12. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18164315 18164315]
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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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Bovine seminal ribonuclease: structure at 1.9 A resolution., Mazzarella L, Capasso S, Demasi D, Di Lorenzo G, Mattia CA, Zagari A, Acta Crystallogr D Biol Crystallogr. 1993 Jul 1;49(Pt 4):389-402. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15299514 15299514]
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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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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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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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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]
[[Category: Bos taurus]]
[[Category: Bos taurus]]
[[Category: Pancreatic ribonuclease]]
[[Category: Pancreatic ribonuclease]]
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[[Category: Nuclease]]
[[Category: Nuclease]]
[[Category: Secreted]]
[[Category: Secreted]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 04:37:27 2008''

Revision as of 01:37, 28 July 2008

Image:3bcm.png

Template:STRUCTURE 3bcm

Crystal Structure of The Unswapped Form of P19A/L28Q/N67D BS-RNase

Template:ABSTRACT PUBMED 18164315

About this Structure

3BCM is a Single protein structure of sequence from Bos taurus. Full crystallographic information is available from OCA.

Reference

The buried diversity of bovine seminal ribonuclease: shape and cytotoxicity of the swapped non-covalent form of the enzyme., Merlino A, Ercole C, Picone D, Pizzo E, Mazzarella L, Sica F, J Mol Biol. 2008 Feb 15;376(2):427-37. Epub 2007 Nov 12. PMID:18164315

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

Bovine seminal ribonuclease: structure at 1.9 A resolution., Mazzarella L, Capasso S, Demasi D, Di Lorenzo G, Mattia CA, Zagari A, Acta Crystallogr D Biol Crystallogr. 1993 Jul 1;49(Pt 4):389-402. PMID:15299514

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

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

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

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

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