1KPH

Crystal Structure of mycolic acid cyclopropane synthase CmaA1 complexed with SAH and DDDMAB


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.240 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.194 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Crystal structures of mycolic acid cyclopropane synthases from Mycobacterium tuberculosis

Huang, C.-C.Smith, C.V.Glickman, M.S.Jacobs Jr., W.R.Sacchettini, J.C.

(2002) J Biol Chem 277: 11559-11569

  • DOI: https://doi.org/10.1074/jbc.M111698200
  • Primary Citation of Related Structures:  
    1KP9, 1KPG, 1KPH, 1KPI, 1L1E

  • PubMed Abstract: 

    Mycolic acids are major components of the cell wall of Mycobacterium tuberculosis. Several studies indicate that functional groups in the acyl chain of mycolic acids are important for pathogenesis and persistence. There are at least three mycolic acid cyclopropane synthases (PcaA, CmaA1, and CmaA2) that are responsible for these site-specific modifications of mycolic acids. To derive information on the specificity and enzyme mechanism of the family of proteins, the crystal structures of CmaA1, CmaA2, and PcaA were solved to 2-, 2-, and 2.65-A resolution, respectively. All three enzymes have a seven-stranded alpha/beta fold similar to other methyltransferases with the location and interactions with the cofactor S-adenosyl-l-methionine conserved. The structures of the ternary complexes demonstrate the position of the mycolic acid substrate binding site. Close examination of the active site reveals electron density that we believe represents a bicarbonate ion. The structures support the hypothesis that these enzymes catalyze methyl transfer via a carbocation mechanism in which the bicarbonate ion acts as a general base. In addition, comparison of the enzyme structures reveals a possible mechanism for substrate specificity. These structures provide a foundation for rational-drug design, which may lead to the development of new inhibitors effective against persistent bacteria.


  • Organizational Affiliation

    Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843-2128, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
CYCLOPROPANE-FATTY-ACYL-PHOSPHOLIPID SYNTHASE 1
A, B, C, D
287Mycobacterium tuberculosisMutation(s): 0 
Gene Names: cmaA1
EC: 2.1.1.79
UniProt
Find proteins for P9WPB7 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore P9WPB7 
Go to UniProtKB:  P9WPB7
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP9WPB7
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SAH
Query on SAH

Download Ideal Coordinates CCD File 
F [auth A],
I [auth B],
L [auth C],
O [auth D]
S-ADENOSYL-L-HOMOCYSTEINE
C14 H20 N6 O5 S
ZJUKTBDSGOFHSH-WFMPWKQPSA-N
10A
Query on 10A

Download Ideal Coordinates CCD File 
G [auth A],
J [auth B],
M [auth C],
P [auth D]
DIDECYL-DIMETHYL-AMMONIUM
C22 H48 N
JGFDZZLUDWMUQH-UHFFFAOYSA-N
CO3
Query on CO3

Download Ideal Coordinates CCD File 
E [auth A],
H [auth B],
K [auth C],
N [auth D]
CARBONATE ION
C O3
BVKZGUZCCUSVTD-UHFFFAOYSA-L
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.240 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.194 
  • Space Group: P 43
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 77.623α = 90
b = 77.623β = 90
c = 174.878γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement
CNSphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2002-01-11
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2024-02-14
    Changes: Data collection, Database references, Derived calculations