5DUJ

Crystal structure of ldtMt2 in complex with Faropenem adduct


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.17 Å
  • R-Value Free: 0.234 
  • R-Value Work: 0.180 
  • R-Value Observed: 0.183 

Starting Model: experimental
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wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 

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This is version 1.5 of the entry. See complete history


Literature

Non-classical transpeptidases yield insight into new antibacterials.

Kumar, P.Kaushik, A.Lloyd, E.P.Li, S.G.Mattoo, R.Ammerman, N.C.Bell, D.T.Perryman, A.L.Zandi, T.A.Ekins, S.Ginell, S.L.Townsend, C.A.Freundlich, J.S.Lamichhane, G.

(2017) Nat Chem Biol 13: 54-61

  • DOI: https://doi.org/10.1038/nchembio.2237
  • Primary Citation of Related Structures:  
    5DU7, 5DUJ, 5DVP, 5DZJ, 5DZP, 5E1G, 5E1I, 5E51, 5E5L, 5K69

  • PubMed Abstract: 

    Bacterial survival requires an intact peptidoglycan layer, a three-dimensional exoskeleton that encapsulates the cytoplasmic membrane. Historically, the final steps of peptidoglycan synthesis are known to be carried out by D,D-transpeptidases, enzymes that are inhibited by the β-lactams, which constitute >50% of all antibacterials in clinical use. Here, we show that the carbapenem subclass of β-lactams are distinctly effective not only because they inhibit D,D-transpeptidases and are poor substrates for β-lactamases, but primarily because they also inhibit non-classical transpeptidases, namely the L,D-transpeptidases, which generate the majority of linkages in the peptidoglycan of mycobacteria. We have characterized the molecular mechanisms responsible for inhibition of L,D-transpeptidases of Mycobacterium tuberculosis and a range of bacteria including ESKAPE pathogens, and used this information to design, synthesize and test simplified carbapenems with potent antibacterial activity.


  • Organizational Affiliation

    Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
L,D-transpeptidase 2
A, B
370Mycobacterium tuberculosis CDC1551Mutation(s): 0 
Gene Names: ldtBMT2594V735_02606
EC: 2.3.2
UniProt
Find proteins for I6Y9J2 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore I6Y9J2 
Go to UniProtKB:  I6Y9J2
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupI6Y9J2
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.17 Å
  • R-Value Free: 0.234 
  • R-Value Work: 0.180 
  • R-Value Observed: 0.183 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 61.051α = 90
b = 93.929β = 92.72
c = 75.215γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
PHASERphasing
HKL-3000data reduction
SCALAdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted DGFClick on this verticalbar to view details

Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/Office of the DirectorUnited States1DP2OD008459-01

Revision History  (Full details and data files)

  • Version 1.0: 2016-09-28
    Type: Initial release
  • Version 1.1: 2016-11-09
    Changes: Database references
  • Version 1.2: 2016-11-23
    Changes: Database references
  • Version 1.3: 2016-12-28
    Changes: Database references
  • Version 1.4: 2017-09-20
    Changes: Author supporting evidence
  • Version 1.5: 2023-09-27
    Changes: Data collection, Database references, Refinement description