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3fl1
From Proteopedia
| 3fl1, resolution 1.90Å () | |||||||||
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| Ligands: | , , | ||||||||
| Non-Standard Residues: | |||||||||
| Gene: | RNASE1, RNS1 (Bos taurus) | ||||||||
| Activity: | Pancreatic ribonuclease, with EC number 3.1.27.5 | ||||||||
| Related: | 1tq9, 3bcp, 1bsr, 1a2w, 1h8x, 3fkz, 3fl0, 3fl3 | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Contents |
X-ray structure of the non covalent swapped form of the A19P/Q28L/K31C/S32C mutant of bovine pancreatic ribonuclease in complex with 2'-DEOXYCYTIDINE-2'-DEOXYGUANOSINE-3',5'-MONOPHOSPHATE
The cytotoxic action of bovine seminal ribonuclease (BS-RNase) depends on its non-covalent swapped dimeric form (NCD-BS), which presents a compact structure that allows the molecule to escape ribonuclease inhibitor (RI). A key role in the acquisition of this structure has been attributed to the concomitant presence of a proline in position 19 and a leucine in position 28. The introduction of Leu28, Cys31 and Cys32 and, in addition, of Pro19 in the sequence of bovine pancreatic ribonuclease (RNase A) has produced two dimeric variants LCC and PLCC, which do exhibit a cytotoxic activity, though at a much lower level than BS-RNase. The crystal structure analysis of the non-covalent swapped form (NCD) of LCC and PLCC, complexed with the substrate analogue 2'-deoxycytidylyl(3',5')-2'-deoxyguanosine, has revealed that, differently from NCD-BS, the dimers adopt an opened quaternary structure, with the two Leu residues fully exposed to the solvent, that does not hinder the binding of RI. Similar results have been obtained for a third mutant of the pancreatic enzyme, engineered with the hinge peptide sequence of the seminal enzyme (residues 16-22) and the two cysteines in position 31 and 32, but lacking the hydrophobic Leu residue in position 28. The comparison of these three structures with those previously reported for other ribonuclease swapped dimers strongly suggests that, in addition to Pro19 and Leu28, the presence of a glycine at the N-terminal end of the hinge peptide is also important to push the swapped form of RNase A dimer into the compact quaternary organization observed for NCD-BS. (c) 2009 Wiley Periodicals, Inc. Biopolymers, 2009.
Towards an antitumor form of bovine pancreatic ribonuclease: The crystal structure of three non-covalent dimeric mutants., Merlino A, Krauss IR, Perillo M, Mattia CA, Ercole C, Picone D, Vergara A, Sica F, Biopolymers. 2009 Mar 11. PMID:19280639
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
3fl1 is a 2 chain structure with sequence from Bos taurus. Full crystallographic information is available from OCA.
See Also
Reference
- Merlino A, Krauss IR, Perillo M, Mattia CA, Ercole C, Picone D, Vergara A, Sica F. Towards an antitumor form of bovine pancreatic ribonuclease: The crystal structure of three non-covalent dimeric mutants. Biopolymers. 2009 Mar 11. PMID:19280639 doi:10.1002/bip.21183
- Sica F, Di Fiore A, Merlino A, Mazzarella L. Structure and stability of the non-covalent swapped dimer of bovine seminal ribonuclease: an enzyme tailored to evade ribonuclease protein inhibitor. J Biol Chem. 2004 Aug 27;279(35):36753-60. Epub 2004 Jun 9. PMID:15192098 doi:10.1074/jbc.M405655200
- Merlino A, Ercole C, Picone D, Pizzo E, Mazzarella L, Sica F. The buried diversity of bovine seminal ribonuclease: shape and cytotoxicity of the swapped non-covalent form of the enzyme. J Mol Biol. 2008 Feb 15;376(2):427-37. Epub 2007 Nov 12. PMID:18164315 doi:10.1016/j.jmb.2007.11.008
- Di Donato A, Cafaro V, Romeo I, D'Alessio G. Hints on the evolutionary design of a dimeric RNase with special bioactions. Protein Sci. 1995 Aug;4(8):1470-7. PMID:8520472 doi:10.1002/pro.5560040804
Categories: Bos taurus | Pancreatic ribonuclease | Ercole, C. | Krauss, I Russo. | Mattia, C A. | Merlino, A. | Perillo, M. | Picone, D. | Sica, F. | Vergara, A. | 3d-domain swapping | Antitumor activity | Bovine seminal ribonuclease | Endonuclease | Glycation | Glycoprotein | Hydrolase | Non-covalent dimer | Nuclease | Protein mutations and evolution | Quaternary structure flexibility | Secreted
