3B7U

Leukotriene A4 Hydrolase Complexed with KELatorphan


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.217 
  • R-Value Work: 0.170 
  • R-Value Observed: 0.188 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Structure-based dissection of the active site chemistry of leukotriene a4 hydrolase: implications for m1 aminopeptidases and inhibitor design.

Tholander, F.Muroya, A.Roques, B.P.Fournie-Zaluski, M.C.Thunnissen, M.M.Haeggstrom, J.Z.

(2008) Chem Biol 15: 920-929

  • DOI: https://doi.org/10.1016/j.chembiol.2008.07.018
  • Primary Citation of Related Structures:  
    2R59, 3B7R, 3B7S, 3B7T, 3B7U

  • PubMed Abstract: 

    M1 aminopeptidases comprise a large family of biologically important zinc enzymes. We show that peptide turnover by the M1 prototype, leukotriene A4 hydrolase/aminopeptidase, involves a shift in substrate position associated with exchange of zinc coordinating groups, while maintaining the overall coordination geometry. The transition state is stabilized by residues conserved among M1 members and in the final reaction step, Glu-296 of the canonical zinc binding HEXXH motif shuffles a proton from the hydrolytic water to the leaving group. Tripeptide substrates bind along the conserved GXMEN motif, precisely occupying the distance between Glu-271 and Arg-563, whereas the Arg specificity is governed by a narrow S1 pocket capped with Asp-375. Our data provide detailed insights to the active site chemistry of M1 aminopeptidases and will aid in the development of novel enzyme inhibitors.


  • Organizational Affiliation

    Department of Medical Biochemistry and Biophysics, Division of Chemistry II, Karolinska Institute, Stockholm, Sweden.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Leukotriene A-4 hydrolaseA [auth X]616Homo sapiensMutation(s): 0 
Gene Names: LTA4HLTA4
EC: 3.3.2.6
UniProt & NIH Common Fund Data Resources
Find proteins for P09960 (Homo sapiens)
Explore P09960 
Go to UniProtKB:  P09960
PHAROS:  P09960
GTEx:  ENSG00000111144 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP09960
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
KEL
Query on KEL

Download Ideal Coordinates CCD File 
G [auth X]N-[(2R)-2-benzyl-4-(hydroxyamino)-4-oxobutanoyl]-L-alanine
C14 H18 N2 O5
OJCFZTVYDSKXNM-GXSJLCMTSA-N
YB
Query on YB

Download Ideal Coordinates CCD File 
C [auth X],
D [auth X],
E [auth X]
YTTERBIUM (III) ION
Yb
AWSFICBXMUKWSK-UHFFFAOYSA-N
IMD
Query on IMD

Download Ideal Coordinates CCD File 
F [auth X]IMIDAZOLE
C3 H5 N2
RAXXELZNTBOGNW-UHFFFAOYSA-O
ZN
Query on ZN

Download Ideal Coordinates CCD File 
B [auth X]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
ACY
Query on ACY

Download Ideal Coordinates CCD File 
H [auth X]ACETIC ACID
C2 H4 O2
QTBSBXVTEAMEQO-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
KEL PDBBind:  3B7U Ki: 18 (nM) from 1 assay(s)
BindingDB:  3B7U Ki: min: 10, max: 18 (nM) from 2 assay(s)
IC50: min: 5, max: 5.00e+4 (nM) from 2 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.217 
  • R-Value Work: 0.170 
  • R-Value Observed: 0.188 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 77.829α = 90
b = 87.136β = 90
c = 99.191γ = 90
Software Package:
Software NamePurpose
MOSFLMdata reduction
SCALAdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
XFITdata reduction

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-09-16
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2018-03-07
    Changes: Data collection
  • Version 1.3: 2019-11-20
    Changes: Database references, Derived calculations
  • Version 1.4: 2023-08-30
    Changes: Data collection, Database references, Derived calculations, Refinement description