5XKR

Crystal structure of Msmeg3575 in complex with benzoguanamine


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.38 Å
  • R-Value Free: 0.153 
  • R-Value Work: 0.128 
  • R-Value Observed: 0.129 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Selective Deamination of Mutagens by a Mycobacterial Enzyme

Gaded, V.Anand, R.

(2017) J Am Chem Soc 139: 10762-10768

  • DOI: https://doi.org/10.1021/jacs.7b04967
  • Primary Citation of Related Structures:  
    5XKO, 5XKP, 5XKQ, 5XKR

  • PubMed Abstract: 

    Structure-based methods are powerful tools that are being exploited to unravel new functions with therapeutic advantage. Here, we report the discovery of a new class of deaminases, predominantly found in mycobacterial species that act on the commercially important s-triazine class of compounds. The enzyme Msd from Mycobacterium smegmatis was taken as a representative candidate from an evolutionarily conserved subgroup that possesses high density of Mycobacterium deaminases. Biochemical investigation reveals that Msd specifically acts on mutagenic nucleobases such as 5-azacytosine and isoguanine and does not accept natural bases as substrates. Determination of the X-ray structure of Msd to a resolution of 1.9 Å shows that Msd has fine-tuned its active site such that it is a hybrid of a cytosine as well as a guanine deaminase, thereby conferring Msd the ability to expand its repertoire to both purine and pyrimidine-like mutagens. Mapping of active site residues along with X-ray structures with a series of triazine analogues aids in deciphering the mechanism by which Msd proofreads the base milieu for mutagens. The genome location of the enzyme reveals that Msd is part of a conserved cluster that confers the organism with innate resistance toward select xenobiotics by triggering their efflux.


  • Organizational Affiliation

    Department of Chemistry, Indian Institute of Technology Bombay , Powai, Mumbai 400076, India.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
CMP/dCMP deaminase, zinc-binding protein
A, B, C, D
159Mycolicibacterium smegmatis MC2 155Mutation(s): 0 
Gene Names: MSMEG_3575MSMEI_3493
UniProt
Find proteins for A0QY90 (Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155))
Explore A0QY90 
Go to UniProtKB:  A0QY90
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA0QY90
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
BZE
Query on BZE

Download Ideal Coordinates CCD File 
E [auth A],
H [auth B],
P [auth C],
W [auth D]
6-phenyl-1,3,5-triazine-2,4-diamine
C9 H9 N5
GZVHEAJQGPRDLQ-UHFFFAOYSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
G [auth A]
L [auth B]
M [auth B]
N [auth B]
S [auth C]
G [auth A],
L [auth B],
M [auth B],
N [auth B],
S [auth C],
T [auth C],
U [auth C],
X [auth D]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
F [auth A],
I [auth B],
Q [auth C],
V [auth D]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
ACT
Query on ACT

Download Ideal Coordinates CCD File 
J [auth B],
K [auth B],
O [auth C],
R [auth C]
ACETATE ION
C2 H3 O2
QTBSBXVTEAMEQO-UHFFFAOYSA-M
Binding Affinity Annotations 
IDSourceBinding Affinity
BZE Binding MOAD:  5XKR Kd: 7000 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.38 Å
  • R-Value Free: 0.153 
  • R-Value Work: 0.128 
  • R-Value Observed: 0.129 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 53.076α = 90
b = 63.446β = 89.99
c = 108.573γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
HKL-3000data reduction
HKL-3000data scaling
Auto-Rickshawphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Department of Science and Technology, Government of IndiaIndiaEMR/2015/002121 and DST/TM/WTI/2K16/252

Revision History  (Full details and data files)

  • Version 1.0: 2017-08-09
    Type: Initial release
  • Version 1.1: 2017-08-16
    Changes: Database references
  • Version 1.2: 2023-11-22
    Changes: Data collection, Database references, Derived calculations, Refinement description