6BNC

Crystal structure of the intrinsic colistin resistance enzyme ICR(Mc) from Moraxella catarrhalis, catalytic domain, Thr315Ala mutant di-zinc and PEG complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.50 Å
  • R-Value Free: 0.153 
  • R-Value Work: 0.132 
  • R-Value Observed: 0.133 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Substrate Recognition by a Colistin Resistance Enzyme from Moraxella catarrhalis.

Stogios, P.J.Cox, G.Zubyk, H.L.Evdokimova, E.Wawrzak, Z.Wright, G.D.Savchenko, A.

(2018) ACS Chem Biol 13: 1322-1332

  • DOI: https://doi.org/10.1021/acschembio.8b00116
  • Primary Citation of Related Structures:  
    6BNC, 6BND, 6BNE, 6BNF

  • PubMed Abstract: 

    Lipid A phosphoethanolamine (PEtN) transferases render bacteria resistant to the last resort antibiotic colistin. The recent discoveries of pathogenic bacteria harboring plasmid-borne PEtN transferase ( mcr) genes have illustrated the serious potential for wide dissemination of these resistance elements. The origin of mcr-1 is traced to Moraxella species co-occupying environmental niches with Enterobacteriaceae. Here, we describe the crystal structure of the catalytic domain of the chromosomally encoded colistin resistance PEtN transferase, ICR Mc (for intrinsic colistin resistance) of Moraxella catarrhalis. The ICR Mc structure in complex with PEtN reveals key molecular details including specific residues involved in catalysis and PEtN binding. It also demonstrates that ICR Mc catalytic domain dimerization is required for substrate binding. Our structure-guided phylogenetic analysis provides sequence signatures defining potentially colistin-active representatives in this enzyme family. Combined, these results advance the molecular and mechanistic understanding of PEtN transferases and illuminate their origins.


  • Organizational Affiliation

    Center for Structural Genomics of Infectious Diseases (CSGID).


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Phosphoethanolamine transferase
A, B
344Moraxella sp. HMSC061H09Mutation(s): 1 
Gene Names: HMPREF2573_04170
UniProt
Find proteins for A0A1E9VP98 (Moraxella sp. HMSC061H09)
Explore A0A1E9VP98 
Go to UniProtKB:  A0A1E9VP98
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA0A1E9VP98
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
15P
Query on 15P

Download Ideal Coordinates CCD File 
E [auth A]
F [auth A]
G [auth A]
H [auth A]
I [auth A]
E [auth A],
F [auth A],
G [auth A],
H [auth A],
I [auth A],
J [auth A],
K [auth A],
N [auth B],
O [auth B]
POLYETHYLENE GLYCOL (N=34)
C69 H140 O35
VUYXVWGKCKTUMF-UHFFFAOYSA-N
ZN (Subject of Investigation/LOI)
Query on ZN

Download Ideal Coordinates CCD File 
C [auth A],
D [auth A],
L [auth B],
M [auth B]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
P [auth B]CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.50 Å
  • R-Value Free: 0.153 
  • R-Value Work: 0.132 
  • R-Value Observed: 0.133 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 74.051α = 90
b = 154.246β = 90
c = 66.392γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-3000data reduction
HKL-3000data scaling
PHENIXphasing
PHENIXmodel building
Cootmodel building

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesHHSN272201200026C
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesHHSN272201700060C

Revision History  (Full details and data files)

  • Version 1.0: 2018-01-31
    Type: Initial release
  • Version 1.1: 2018-02-14
    Changes: Author supporting evidence
  • Version 1.2: 2018-04-25
    Changes: Data collection, Database references
  • Version 1.3: 2018-05-30
    Changes: Data collection, Database references
  • Version 1.4: 2019-12-11
    Changes: Author supporting evidence