3O0N

Thermotoga maritima Ribonucleotide Reductase, NrdJ, in complex with dTTP and Adenosylcobalamin


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.249 
  • R-Value Work: 0.203 
  • R-Value Observed: 0.205 

Starting Model: experimental
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wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.5 of the entry. See complete history


Literature

Structural Basis for Adenosylcobalamin Activation in AdoCbl-Dependent Ribonucleotide Reductases.

Larsson, K.M.Logan, D.T.Nordlund, P.

(2010) ACS Chem Biol 5: 933-942

  • DOI: https://doi.org/10.1021/cb1000845
  • Primary Citation of Related Structures:  
    3O0N, 3O0O, 3O0Q

  • PubMed Abstract: 

    Class II ribonucleotide reductases (RNR) catalyze the formation of an essential thiyl radical by homolytic cleavage of the Co-C bond in their adenosylcobalamin (AdoCbl) cofactor. Several mechanisms for the dramatic acceleration of Co-C bond cleavage in AdoCbl-dependent enzymes have been advanced, but no consensus yet exists. We present the structure of the class II RNR from Thermotoga maritima in three complexes: (i) with allosteric effector dTTP, substrate GDP, and AdoCbl; (ii) with dTTP and AdoCbl; (iii) with dTTP, GDP, and adenosine. Comparison of these structures gives the deepest structural insights so far into the mechanism of radical generation and transfer for AdoCbl-dependent RNR. AdoCbl binds to the active site pocket, shielding the substrate, transient 5'-deoxyadenosyl radical and nascent thiyl radical from solution. The e-propionamide side chain of AdoCbl forms hydrogen bonds directly to the α-phosphate group of the substrate. This interaction appears to cause a "locking-in" of the cofactor, and it is the first observation of a direct cofactor-substrate interaction in an AdoCbl-dependent enzyme. The structures support an ordered sequential reaction mechanism with release or relaxation of AdoCbl on each catalytic cycle. A conformational change of the AdoCbl adenosyl ribose is required to allow hydrogen transfer to the catalytic thiol group. Previously proposed mechanisms for radical transfer in B12-dependent enzymes cannot fully explain the transfer in class II RNR, suggesting that it may form a separate class that differs from the well-characterized eliminases and mutases.


  • Organizational Affiliation

    Department of Biochemistry and Biophysics, Stockholm University, S-106 91 Stockholm, Sweden.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Ribonucleoside-diphosphate reductase
A, B
644Thermotoga maritimaMutation(s): 0 
Gene Names: nrdJTM_0118
EC: 1.17.4.1
UniProt
Find proteins for O33839 (Thermotoga maritima)
Explore O33839 
Go to UniProtKB:  O33839
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO33839
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 6 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
B12
Query on B12

Download Ideal Coordinates CCD File 
I [auth B]COBALAMIN
C62 H89 Co N13 O14 P
LKVIQTCSMMVGFU-DWSMJLPVSA-N
TTP
Query on TTP

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C [auth A],
H [auth B]
THYMIDINE-5'-TRIPHOSPHATE
C10 H17 N2 O14 P3
NHVNXKFIZYSCEB-XLPZGREQSA-N
5AD
Query on 5AD

Download Ideal Coordinates CCD File 
J [auth B]5'-DEOXYADENOSINE
C10 H13 N5 O3
XGYIMTFOTBMPFP-KQYNXXCUSA-N
CO
Query on CO

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D [auth A]COBALT (II) ION
Co
XLJKHNWPARRRJB-UHFFFAOYSA-N
CL
Query on CL

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E [auth A]CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
MG
Query on MG

Download Ideal Coordinates CCD File 
F [auth A],
G [auth B]
MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.249 
  • R-Value Work: 0.203 
  • R-Value Observed: 0.205 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 119.01α = 90
b = 123.82β = 103.1
c = 106.44γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
REFMACrefinement
ProDCdata collection
XDSdata reduction
XSCALEdata scaling
REFMACphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-07-28
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2012-10-24
    Changes: Non-polymer description
  • Version 1.3: 2017-11-08
    Changes: Advisory, Refinement description
  • Version 1.4: 2019-07-17
    Changes: Data collection, Refinement description
  • Version 1.5: 2023-09-06
    Changes: Advisory, Data collection, Database references, Derived calculations, Refinement description