3FGN

Crystal structure of dethiobiotin synthetase in Mycobacterium tuberculosis


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.253 
  • R-Value Work: 0.214 
  • R-Value Observed: 0.216 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structural characterization of the Mycobacterium tuberculosis biotin biosynthesis enzymes 7,8-diaminopelargonic acid synthase and dethiobiotin synthetase .

Dey, S.Lane, J.M.Lee, R.E.Rubin, E.J.Sacchettini, J.C.

(2010) Biochemistry 49: 6746-6760

  • DOI: https://doi.org/10.1021/bi902097j
  • Primary Citation of Related Structures:  
    3BV0, 3DOD, 3DRD, 3DU4, 3FGN, 3FMF, 3FMI, 3FPA, 3LV2

  • PubMed Abstract: 

    Mycobacterium tuberculosis (Mtb) depends on biotin synthesis for survival during infection. In the absence of biotin, disruption of the biotin biosynthesis pathway results in cell death rather than growth arrest, an unusual phenotype for an Mtb auxotroph. Humans lack the enzymes for biotin production, making the proteins of this essential Mtb pathway promising drug targets. To this end, we have determined the crystal structures of the second and third enzymes of the Mtb biotin biosynthetic pathway, 7,8-diaminopelargonic acid synthase (DAPAS) and dethiobiotin synthetase (DTBS), at respective resolutions of 2.2 and 1.85 A. Superimposition of the DAPAS structures bound either to the SAM analogue sinefungin or to 7-keto-8-aminopelargonic acid (KAPA) allowed us to map the putative binding site for the substrates and to propose a mechanism by which the enzyme accommodates their disparate structures. Comparison of the DTBS structures bound to the substrate 7,8-diaminopelargonic acid (DAPA) or to ADP and the product dethiobiotin (DTB) permitted derivation of an enzyme mechanism. There are significant differences between the Mtb enzymes and those of other organisms; the Bacillus subtilis DAPAS, presented here at a high resolution of 2.2 A, has active site variations and the Escherichia coli and Helicobacter pylori DTBS have alterations in their overall folds. We have begun to exploit the unique characteristics of the Mtb structures to design specific inhibitors against the biotin biosynthesis pathway in Mtb.


  • Organizational Affiliation

    Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Dethiobiotin synthetase
A, B, C, D
251Mycobacterium tuberculosisMutation(s): 0 
Gene Names: bioDMT1621MTCY336.33cRv1570
EC: 6.3.3.3
UniProt
Find proteins for P9WPQ5 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore P9WPQ5 
Go to UniProtKB:  P9WPQ5
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP9WPQ5
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.253 
  • R-Value Work: 0.214 
  • R-Value Observed: 0.216 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 55.383α = 90
b = 104.684β = 90
c = 151.392γ = 90
Software Package:
Software NamePurpose
CrystalCleardata collection
SHARPphasing
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-06-30
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Version format compliance
  • Version 1.2: 2024-02-21
    Changes: Data collection, Database references