3OEC

Crystal structure of carveol dehydrogenase from Mycobacterium thermoresistibile


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.233 
  • R-Value Work: 0.176 
  • R-Value Observed: 0.179 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

Mycofactocin-associated mycobacterial dehydrogenases with non-exchangeable NAD cofactors.

Haft, D.H.Pierce, P.G.Mayclin, S.J.Sullivan, A.Gardberg, A.S.Abendroth, J.Begley, D.W.Phan, I.Q.Staker, B.L.Myler, P.J.Marathias, V.M.Lorimer, D.D.Edwards, T.E.

(2017) Sci Rep 7: 41074-41074

  • DOI: https://doi.org/10.1038/srep41074
  • Primary Citation of Related Structures:  
    3OEC, 3PGX, 3PXX, 3S55, 3SX2, 3T7C, 3TSC, 4RGB, 5EJ2

  • PubMed Abstract: 

    During human infection, Mycobacterium tuberculosis (Mtb) survives the normally bacteriocidal phagosome of macrophages. Mtb and related species may be able to combat this harsh acidic environment which contains reactive oxygen species due to the mycobacterial genomes encoding a large number of dehydrogenases. Typically, dehydrogenase cofactor binding sites are open to solvent, which allows NAD/NADH exchange to support multiple turnover. Interestingly, mycobacterial short chain dehydrogenases/reductases (SDRs) within family TIGR03971 contain an insertion at the NAD binding site. Here we present crystal structures of 9 mycobacterial SDRs in which the insertion buries the NAD cofactor except for a small portion of the nicotinamide ring. Line broadening and STD-NMR experiments did not show NAD or NADH exchange on the NMR timescale. STD-NMR demonstrated binding of the potential substrate carveol, the potential product carvone, the inhibitor tricyclazol, and an external redox partner 2,6-dichloroindophenol (DCIP). Therefore, these SDRs appear to contain a non-exchangeable NAD cofactor and may rely on an external redox partner, rather than cofactor exchange, for multiple turnover. Incidentally, these genes always appear in conjunction with the mftA gene, which encodes the short peptide MftA, and with other genes proposed to convert MftA into the external redox partner mycofactocin.


  • Organizational Affiliation

    National Institutes of Health (NIH), Bethesda, MD 20892, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Carveol dehydrogenase (MythA.01326.c, A0R518 homolog)
A, B, C, D
317Mycolicibacterium thermoresistibileMutation(s): 0 
EC: 1.1.1.234
UniProt
Find proteins for E1C9L4 (Mycolicibacterium thermoresistibile)
Explore E1C9L4 
Go to UniProtKB:  E1C9L4
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupE1C9L4
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

Unit Cell:
Length ( Å )Angle ( ˚ )
a = 67.86α = 90
b = 120.57β = 94.05
c = 134.56γ = 90
Software Package:
Software NamePurpose
StructureStudiodata collection
PHASERphasing
REFMACrefinement
XDSdata reduction
XSCALEdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-09-01
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2015-03-11
    Changes: Database references
  • Version 1.3: 2015-04-15
    Changes: Database references
  • Version 1.4: 2017-02-08
    Changes: Database references
  • Version 1.5: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description