6C4C

Crystal structure of 3-nitropropionate modified isocitrate lyase from Mycobacterium tuberculosis with glyoxylate and pyruvate


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.247 
  • R-Value Work: 0.192 
  • R-Value Observed: 0.193 

wwPDB Validation   3D Report Full Report


This is version 3.0 of the entry. See complete history


Literature

The Nitro Group as a Masked Electrophile in Covalent Enzyme Inhibition.

Ray, S.Kreitler, D.F.Gulick, A.M.Murkin, A.S.

(2018) ACS Chem Biol 13: 1470-1473

  • DOI: https://doi.org/10.1021/acschembio.8b00225
  • Primary Citation of Related Structures:  
    6C4A, 6C4C

  • PubMed Abstract: 

    We report the unprecedented reaction between a nitroalkane and an active-site cysteine residue to yield a thiohydroximate adduct. Structural and kinetic evidence suggests the nitro group is activated by conversion to its nitronic acid tautomer within the active site. The nitro group, therefore, shows promise as a masked electrophile in the design of covalent inhibitors targeting binding pockets with appropriately placed cysteine and general acid residues.


  • Organizational Affiliation

    Department of Chemistry , University at Buffalo , Buffalo , New York 14260-3000 , United States.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Isocitrate lyase 1
A, B, C, D, E
A, B, C, D, E, F, G, H
442Mycobacterium tuberculosis str. Erdman = ATCC 35801Mutation(s): 0 
Gene Names: icl1ERDMAN_0512Q643_00485
EC: 4.1.3.1 (PDB Primary Data), 4.1.3.30 (PDB Primary Data)
UniProt
Find proteins for P9WKK7 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore P9WKK7 
Go to UniProtKB:  P9WKK7
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP9WKK7
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
3NP
Query on 3NP

Download Ideal Coordinates CCD File 
X [auth E]3-NITROPROPANOIC ACID
C3 H5 N O4
WBLZUCOIBUDNBV-UHFFFAOYSA-N
PYR
Query on PYR

Download Ideal Coordinates CCD File 
AA [auth G],
L [auth B],
O [auth C],
U [auth E],
Y [auth F]
PYRUVIC ACID
C3 H4 O3
LCTONWCANYUPML-UHFFFAOYSA-N
GLV
Query on GLV

Download Ideal Coordinates CCD File 
EA [auth H],
I [auth A],
R [auth D]
GLYOXYLIC ACID
C2 H2 O3
HHLFWLYXYJOTON-UHFFFAOYSA-N
MG
Query on MG

Download Ideal Coordinates CCD File 
BA [auth G]
CA [auth G]
DA [auth H]
FA [auth H]
GA [auth H]
BA [auth G],
CA [auth G],
DA [auth H],
FA [auth H],
GA [auth H],
J [auth A],
K [auth A],
M [auth B],
N [auth B],
P [auth C],
Q [auth C],
S [auth D],
T [auth D],
V [auth E],
W [auth E],
Z [auth F]
MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
EJA
Query on EJA
A, B, C, D, E
A, B, C, D, E, F, G, H
L-PEPTIDE LINKINGC6 H10 N2 O5 SCYS
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.247 
  • R-Value Work: 0.192 
  • R-Value Observed: 0.193 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 143.76α = 90
b = 87.13β = 116.55
c = 152.99γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XSCALEdata scaling
PDB_EXTRACTdata extraction
PHASERphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Science Foundation (NSF, United States)United StatesCHE1255136
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesGM116957

Revision History  (Full details and data files)

  • Version 1.0: 2018-06-06
    Type: Initial release
  • Version 1.1: 2018-06-27
    Changes: Data collection, Database references
  • Version 2.0: 2022-03-16
    Changes: Atomic model, Author supporting evidence, Database references, Derived calculations, Structure summary
  • Version 2.1: 2023-10-04
    Changes: Data collection, Refinement description
  • Version 3.0: 2023-11-15
    Changes: Atomic model, Data collection, Derived calculations