5CDH

Structure of Legionella pneumophila Histidine Acid Phosphatase complexed with L(+)-tartrate


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.224 
  • R-Value Work: 0.186 
  • R-Value Observed: 0.188 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Crystal structure and tartrate inhibition of Legionella pneumophila histidine acid phosphatase.

Dhatwalia, R.Singh, H.Reilly, T.J.Tanner, J.J.

(2015) Arch Biochem Biophys 585: 32-38

  • DOI: https://doi.org/10.1016/j.abb.2015.09.010
  • Primary Citation of Related Structures:  
    5CDH

  • PubMed Abstract: 

    Histidine acid phosphatases (HAPs) utilize a nucleophilic histidine residue to catalyze the transfer of a phosphoryl group from phosphomonoesters to water. HAPs function as protein phosphatases and pain suppressors in mammals, are essential for Giardia lamblia excystation, and contribute to virulence of the category A pathogen Francisella tularensis. Herein we report the first crystal structure and steady-state kinetics measurements of the HAP from Legionella pneumophila (LpHAP), also known as Legionella major acid phosphatase. The structure of LpHAP complexed with the inhibitor l(+)-tartrate was determined at 2.0 Å resolution. Kinetics assays show that l(+)-tartrate is a 50-fold more potent inhibitor of LpHAP than of other HAPs. Electrostatic potential calculations provide insight into the basis for the enhanced tartrate potency: the tartrate pocket of LpHAP is more positive than other HAPs because of the absence of an ion pair partner for the second Arg of the conserved RHGXRXP HAP signature sequence. The structure also reveals that LpHAP has an atypically expansive active site entrance and lacks the nucleotide substrate base clamp found in other HAPs. These features imply that nucleoside monophosphates may not be preferred substrates. Kinetics measurements confirm that AMP is a relatively inefficient in vitro substrate of LpHAP.


  • Organizational Affiliation

    Department of Chemistry, University of Missouri-Columbia, Columbia, MO 65211, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Major acid phosphatase
A, B, C, D, E
A, B, C, D, E, F, G, H
336Legionella pneumophilaMutation(s): 0 
Gene Names: map
UniProt
Find proteins for Q9APF7 (Legionella pneumophila)
Explore Q9APF7 
Go to UniProtKB:  Q9APF7
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9APF7
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
1PE
Query on 1PE

Download Ideal Coordinates CCD File 
CA [auth H]
J [auth A]
K [auth A]
L [auth A]
M [auth A]
CA [auth H],
J [auth A],
K [auth A],
L [auth A],
M [auth A],
O [auth B],
P [auth B],
R [auth C],
T [auth D],
V [auth E],
W [auth E],
X [auth E],
Z [auth F]
PENTAETHYLENE GLYCOL
C10 H22 O6
JLFNLZLINWHATN-UHFFFAOYSA-N
TLA
Query on TLA

Download Ideal Coordinates CCD File 
AA [auth G]
BA [auth H]
I [auth A]
N [auth B]
Q [auth C]
AA [auth G],
BA [auth H],
I [auth A],
N [auth B],
Q [auth C],
S [auth D],
U [auth E],
Y [auth F]
L(+)-TARTARIC ACID
C4 H6 O6
FEWJPZIEWOKRBE-JCYAYHJZSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
TLA Binding MOAD:  5CDH Ki: 4300 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.224 
  • R-Value Work: 0.186 
  • R-Value Observed: 0.188 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 217.889α = 90
b = 134.274β = 127.46
c = 135.78γ = 90
Software Package:
Software NamePurpose
SCALEPACKdata scaling
PHENIXrefinement
PDB_EXTRACTdata extraction
HKL-2000data reduction
MOLREPphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

  • Released Date: 2016-01-27 
  • Deposition Author(s): Tanner, J.J.

Revision History  (Full details and data files)

  • Version 1.0: 2016-01-27
    Type: Initial release
  • Version 1.1: 2023-09-27
    Changes: Data collection, Database references, Derived calculations, Refinement description