4WP3

Crystal Structure of Adenylyl cyclase from Mycobacterium avium Ma1120 wild type


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.213 
  • R-Value Work: 0.178 
  • R-Value Observed: 0.180 

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This is version 1.1 of the entry. See complete history


Literature

Autoinhibitory mechanism and activity-related structural changes in a mycobacterial adenylyl cyclase

Barathy, D.V.Bharambe, N.G.Syed, W.Zaveri, A.Visweswariah, S.S.Cola sigmaf o, M.Misquith, S.Suguna, K.

(2015) J Struct Biol 190: 304-313

  • DOI: https://doi.org/10.1016/j.jsb.2015.04.013
  • Primary Citation of Related Structures:  
    4WP3, 4WP8, 4WP9, 4WPA

  • PubMed Abstract: 

    An adenylyl cyclase from Mycobacterium avium, Ma1120, is a functional orthologue of a pseudogene Rv1120c from Mycobacterium tuberculosis. We report the crystal structure of Ma1120 in a monomeric form and its truncated construct as a dimer. Ma1120 exists as a monomer in solution and crystallized as a monomer in the absence of substrate or inhibitor. An additional α-helix present at the N-terminus of the monomeric structure blocks the active site by interacting with the substrate binding residues and occupying the dimer interface region. However, the enzyme has been found to be active in solution, indicating the movement of the helix away from the interface to facilitate the formation of active dimers in conditions favourable for catalysis. Thus, the N-terminal helix of Ma1120 keeps the enzyme in an autoinhibited state when it is not active. Deletion of this helix enabled us to crystallize the molecule as an active homodimer in the presence of a P-site inhibitor 2',5'-dideoxy-3'-ATP, or pyrophosphate along with metal ions. The substrate specifying lysine residue plays a dual role of interacting with the substrate and stabilizing the dimer. The dimerization loop region harbouring the second substrate specifying residue, an aspartate, shows significant differences in conformation and position between the monomeric and dimeric structures. Thus, this study has not only revealed that significant structural transitions are required for the interconversion of the inactive and the active forms of the enzyme, but also provided precise nature of these transitions.


  • Organizational Affiliation

    Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560 012, India.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Ma1120
A, B, C, D, E
A, B, C, D, E, F
210Mycobacterium aviumMutation(s): 0 
Gene Names: cya1120
EC: 4.6.1.1
UniProt
Find proteins for Q5UFR5 (Mycobacterium avium)
Explore Q5UFR5 
Go to UniProtKB:  Q5UFR5
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ5UFR5
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.213 
  • R-Value Work: 0.178 
  • R-Value Observed: 0.180 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 97.79α = 90
b = 53.87β = 94.77
c = 111.2γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-09-02
    Type: Initial release
  • Version 1.1: 2023-11-08
    Changes: Data collection, Database references, Derived calculations, Refinement description