1JS3

Crystal structure of dopa decarboxylase in complex with the inhibitor carbidopa


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.25 Å
  • R-Value Free: 0.187 
  • R-Value Work: 0.144 
  • R-Value Observed: 0.144 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Structural insight into Parkinson's disease treatment from drug-inhibited DOPA decarboxylase.

Burkhard, P.Dominici, P.Borri-Voltattorni, C.Jansonius, J.N.Malashkevich, V.N.

(2001) Nat Struct Biol 8: 963-967

  • DOI: https://doi.org/10.1038/nsb1101-963
  • Primary Citation of Related Structures:  
    1JS3, 1JS6

  • PubMed Abstract: 

    DOPA decarboxylase (DDC) is responsible for the synthesis of the key neurotransmitters dopamine and serotonin via decarboxylation of L-3,4-dihydroxyphenylalanine (L-DOPA) and L-5-hydroxytryptophan, respectively. DDC has been implicated in a number of clinic disorders, including Parkinson's disease and hypertension. Peripheral inhibitors of DDC are currently used to treat these diseases. We present the crystal structures of ligand-free DDC and its complex with the anti-Parkinson drug carbiDOPA. The inhibitor is bound to the enzyme by forming a hydrazone linkage with the cofactor, and its catechol ring is deeply buried in the active site cleft. The structures provide the molecular basis for the development of new inhibitors of DDC with better pharmacological characteristics.


  • Organizational Affiliation

    M.E. Müller Institute for Structural Biology, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland. Peter.Burkhard@unibas.ch


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
DOPA decarboxylase
A, B
486Sus scrofaMutation(s): 0 
EC: 4.1.1.28
UniProt
Find proteins for P80041 (Sus scrofa)
Explore P80041 
Go to UniProtKB:  P80041
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP80041
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
PLP
Query on PLP

Download Ideal Coordinates CCD File 
E [auth A],
I [auth B]
PYRIDOXAL-5'-PHOSPHATE
C8 H10 N O6 P
NGVDGCNFYWLIFO-UHFFFAOYSA-N
142
Query on 142

Download Ideal Coordinates CCD File 
F [auth A],
J [auth B]
CARBIDOPA
C10 H14 N2 O4
TZFNLOMSOLWIDK-JTQLQIEISA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
C [auth A],
D [auth A],
G [auth B],
H [auth B]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.25 Å
  • R-Value Free: 0.187 
  • R-Value Work: 0.144 
  • R-Value Observed: 0.144 
  • Space Group: P 62
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 154.36α = 90
b = 154.36β = 90
c = 86.78γ = 120
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
SHARPphasing
DMmodel building
CNSrefinement
DMphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2001-10-26
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.3: 2024-02-07
    Changes: Data collection, Database references, Derived calculations, Structure summary