3B7I

Crystal structure of the S228A mutant of the aminopeptidase from Vibrio proteolyticus in complex with leucine phosphonic acid


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.75 Å
  • R-Value Free: 0.209 
  • R-Value Work: 0.177 
  • R-Value Observed: 0.178 

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This is version 1.4 of the entry. See complete history


Literature

Zinc coordination geometry and ligand binding affinity: the structural and kinetic analysis of the second-shell serine 228 residue and the methionine 180 residue of the aminopeptidase from Vibrio proteolyticus.

Ataie, N.J.Hoang, Q.Q.Zahniser, M.P.Tu, Y.Milne, A.Petsko, G.A.Ringe, D.

(2008) Biochemistry 47: 7673-7683

  • DOI: https://doi.org/10.1021/bi702188e
  • Primary Citation of Related Structures:  
    3B35, 3B3C, 3B3S, 3B3T, 3B3V, 3B3W, 3B7I

  • PubMed Abstract: 

    The chemical properties of zinc make it an ideal metal to study the role of coordination strain in enzymatic rate enhancement. The zinc ion and the protein residues that are bound directly to the zinc ion represent a functional charge/dipole complex, and polarization of this complex, which translates to coordination distortion, may tune electrophilicity, and hence, reactivity. Conserved protein residues outside of the charge/dipole complex, such as second-shell residues, may play a role in supporting the electronic strain produced as a consequence of functional polarization. To test the correlation between charge/dipole polarity and ligand binding affinity, structure-function studies were carried out on the dizinc aminopeptidase from Vibrio proteolyticus. Alanine substitutions of S228 and M180 resulted in catalytically diminished enzymes whose crystal structures show very little change in the positions of the metal ions and the protein residues. However, more detailed inspections of the crystal structures show small positional changes that account for differences in the zinc ion coordination geometry. Measurements of the binding affinity of leucine phosphonic acid, a transition state analogue, and leucine, a product, show a correlation between coordination geometry and ligand binding affinity. These results suggest that the coordination number and polarity may tune the electrophilicity of zinc. This may have provided the evolving enzyme with the ability to discriminate between reaction coordinate species.


  • Organizational Affiliation

    Rosenstiel Basic Medical Sciences Research Center and Department of Biochemistry, Program in Biochemistry and Biophysics, Brandeis University, 415 South Street, Waltham, Massachusetts 02454, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Bacterial leucyl aminopeptidase291Vibrio proteolyticusMutation(s): 1 
Gene Names: AAP
EC: 3.4.11.10
UniProt
Find proteins for Q01693 (Vibrio proteolyticus)
Explore Q01693 
Go to UniProtKB:  Q01693
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ01693
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 6 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
PLU
Query on PLU

Download Ideal Coordinates CCD File 
H [auth A]LEUCINE PHOSPHONIC ACID
C5 H14 N O3 P
HGCAUCAWEADMPM-RXMQYKEDSA-N
LEU
Query on LEU

Download Ideal Coordinates CCD File 
I [auth A]LEUCINE
C6 H13 N O2
ROHFNLRQFUQHCH-YFKPBYRVSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
B [auth A],
C [auth A]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
SCN
Query on SCN

Download Ideal Coordinates CCD File 
G [auth A]THIOCYANATE ION
C N S
ZMZDMBWJUHKJPS-UHFFFAOYSA-M
K
Query on K

Download Ideal Coordinates CCD File 
D [auth A]POTASSIUM ION
K
NPYPAHLBTDXSSS-UHFFFAOYSA-N
NA
Query on NA

Download Ideal Coordinates CCD File 
E [auth A],
F [auth A]
SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
LEU Binding MOAD:  3B7I Ki: 6.50e+4 (nM) from 1 assay(s)
PLU Binding MOAD:  3B7I Ki: 1500 (nM) from 1 assay(s)
LPA PDBBind:  3B7I Ki: 1500 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.75 Å
  • R-Value Free: 0.209 
  • R-Value Work: 0.177 
  • R-Value Observed: 0.178 
  • Space Group: P 61 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 109.907α = 90
b = 109.907β = 90
c = 91.095γ = 120
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
MOLREPphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-11-27
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-10-25
    Changes: Refinement description
  • Version 1.3: 2021-10-20
    Changes: Database references, Derived calculations
  • Version 1.4: 2023-08-30
    Changes: Data collection, Refinement description