6K26

Crystal structure of Vibrio cholerae methionine aminopeptidase


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.208 
  • R-Value Work: 0.166 
  • R-Value Observed: 0.168 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Methionine aminopeptidases with short sequence inserts within the catalytic domain are differentially inhibited: Structural and biochemical studies of three proteins from Vibrio spp.

Pillalamarri, V.Reddy, C.G.Bala, S.C.Jangam, A.Kutty, V.V.Addlagatta, A.

(2020) Eur J Med Chem 209: 112883-112883

  • DOI: https://doi.org/10.1016/j.ejmech.2020.112883
  • Primary Citation of Related Structures:  
    6K26, 6KSG, 6LH7

  • PubMed Abstract: 

    Methionine aminopeptidases (MetAPs) have been recognized as drug targets and have been extensively studied for discovery of selective inhibitors. MetAPs are essential enzymes in all living cells. While most prokaryotes contain a single gene, some prokaryotes and all eukaryotes including human have redundancy. Due to the similarity in the active sites of the MetAP enzyme between the pathogens and human limited the success of discovering selective inhibitors. We recently have discovered that MetAPs with small inserts within the catalytic domain to have different susceptibilities against some inhibitors compared to those that do not have. Using this clue we used bioinformatic tools to identify new variants of MetAPs with inserts in pathogenic species. Two new isoforms were identified in Vibrio species with two and three inserts in addition to an isoform without any insert. Multiple sequence alignment suggested that inserts are conserved in several of the Vibrio species. Two of the three inserts are common between two and three insert isoforms. One of the inserts is identified to have "NNKNN" motif that is similar to well-characterized quorum sensing peptide, "NNWNN". Another insert is predicted to have a posttranslational modification site. Three Vibrio proteins were cloned, expressed, purified, enzyme kinetics established and inhibitor screening has been performed. Several of the pyridinylpyrimidine derivatives selectively inhibited MetAPs with inserts compared to those that do not have, including the human enzyme. Crystal structure and molecular modeling studies provide the molecular basis for selective inhibition.


  • Organizational Affiliation

    Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India; CSIR-Indian Institute of Chemical Technology, Department of Applied Biology, Hyderabad, Telangana, 500007, India.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Methionine aminopeptidase
A, B
300Vibrio choleraeMutation(s): 0 
Gene Names: map
EC: 3.4.11.18
UniProt
Find proteins for Q9KPV1 (Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961))
Explore Q9KPV1 
Go to UniProtKB:  Q9KPV1
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9KPV1
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.208 
  • R-Value Work: 0.166 
  • R-Value Observed: 0.168 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 49.529α = 90
b = 50.01β = 97.25
c = 131.086γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data scaling
MOLREPphasing
PDB_EXTRACTdata extraction
Cootmodel building
HKL-2000data reduction
HKL-3000data collection

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Department of Science & Technology (India)IndiaEMR/2015/000461

Revision History  (Full details and data files)

  • Version 1.0: 2020-05-20
    Type: Initial release
  • Version 1.1: 2020-12-02
    Changes: Database references, Derived calculations
  • Version 1.2: 2023-11-22
    Changes: Data collection, Database references, Refinement description