1TQ9

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


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.269 
  • R-Value Work: 0.206 
  • R-Value Observed: 0.212 

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This is version 1.3 of the entry. See complete history


Literature

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.

(2004) J Biol Chem 279: 36753-36760

  • DOI: https://doi.org/10.1074/jbc.M405655200
  • Primary Citation of Related Structures:  
    1TQ9

  • PubMed Abstract: 

    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.


  • Organizational Affiliation

    Dipartimento di Chimica, Università degli Studi di Napoli Federico II, Via Cynthia, 80126 Naples, Italy.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Ribonuclease, seminal
A, B
124Bos taurusMutation(s): 2 
EC: 3.1.27.5
UniProt
Find proteins for P00669 (Bos taurus)
Explore P00669 
Go to UniProtKB:  P00669
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00669
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
CPA
Query on CPA

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
2'-DEOXYCYTIDINE-2'-DEOXYADENOSINE-3',5'-MONOPHOSPHATE
C19 H25 N8 O9 P
LYWWDKIADIGKTH-IDMWBNCISA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
YCM
Query on YCM
A, B
L-PEPTIDE LINKINGC5 H10 N2 O3 SCYS
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.269 
  • R-Value Work: 0.206 
  • R-Value Observed: 0.212 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 41.471α = 90
b = 69.689β = 90
c = 110.804γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
SCALEPACKdata scaling
X-PLORmodel building
X-PLORrefinement
HKL-2000data reduction
X-PLORphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-09-14
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-10-25
    Changes: Data collection, Database references, Derived calculations, Refinement description