1IYK

Crystal structure of candida albicans N-myristoyltransferase with myristoyl-COA and peptidic inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.244 
  • R-Value Work: 0.192 
  • R-Value Observed: 0.206 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Crystal Structures of Candida albicans N-Myristoyltransferase with Two Distinct Inhibitors

Sogabe, S.Masubuchi, M.Sakata, K.Fukami, T.A.Morikami, K.Shiratori, Y.Ebiike, H.Kawasaki, K.Aoki, Y.Shimma, N.D'Arcy, A.Winkler, F.K.Banner, D.W.Ohtsuka, T.

(2002) Chem Biol 9: 1119-1128

  • DOI: https://doi.org/10.1016/s1074-5521(02)00240-5
  • Primary Citation of Related Structures:  
    1IYK, 1IYL

  • PubMed Abstract: 

    Myristoyl-CoA:protein N-myristoyltransferase (Nmt) is a monomeric enzyme that catalyzes the transfer of the fatty acid myristate from myristoyl-CoA to the N-terminal glycine residue of a variety of eukaryotic and viral proteins. Genetic and biochemical studies have established that Nmt is an attractive target for antifungal drugs. We present here crystal structures of C. albicans Nmt complexed with two classes of inhibitor competitive for peptide substrates. One is a peptidic inhibitor designed from the peptide substrate; the other is a nonpeptidic inhibitor having a benzofuran core. Both inhibitors are bound into the same binding groove, generated by some structural rearrangements of the enzyme, with the peptidic inhibitor showing a substrate-like binding mode and the nonpeptidic inhibitor binding differently. Further, site-directed mutagenesis for C. albicans Nmt has been utilized in order to define explicitly which amino acids are critical for inhibitor binding. The results suggest that the enzyme has some degree of flexibility for substrate binding and provide valuable information for inhibitor design.


  • Organizational Affiliation

    Nippon Roche Research Center, 200 Kajiwara, Kamakura, Kanagawa 247-8530, Japan. satoshi.sogabe@roche.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
MYRISTOYL-COA:PROTEIN N-MYRISTOYLTRANSFERASE
A, B
392Candida albicansMutation(s): 0 
EC: 2.3.1.97
UniProt
Find proteins for P30418 (Candida albicans (strain SC5314 / ATCC MYA-2876))
Explore P30418 
Go to UniProtKB:  P30418
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP30418
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
MYA
Query on MYA

Download Ideal Coordinates CCD File 
C [auth A],
E [auth B]
TETRADECANOYL-COA
C35 H62 N7 O17 P3 S
DUAFKXOFBZQTQE-QSGBVPJFSA-N
MIM
Query on MIM

Download Ideal Coordinates CCD File 
D [auth A],
F [auth B]
[CYCLOHEXYLETHYL]-[[[[4-[2-METHYL-1-IMIDAZOLYL-BUTYL]PHENYL]ACETYL]-SERYL]-LYSINYL]-AMINE
C33 H52 N6 O4
WHLPIOSHBKQGHA-KYJUHHDHSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
MIM BindingDB:  1IYK Ki: 31 (nM) from 1 assay(s)
Binding MOAD:  1IYK Ki: 250 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.244 
  • R-Value Work: 0.192 
  • R-Value Observed: 0.206 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 58.696α = 90
b = 95.334β = 90
c = 176.549γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
SHARPphasing
CNXrefinement

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2002-12-30
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Derived calculations, Version format compliance
  • Version 1.3: 2011-11-09
    Changes: Advisory
  • Version 1.4: 2023-12-27
    Changes: Data collection, Database references, Derived calculations