1D7V

CRYSTAL STRUCTURE OF THE COMPLEX OF 2,2-DIALKYLGLYCINE DECARBOXYLASE WITH NMA


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Work: 0.185 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Crystal structures of dialkylglycine decarboxylase inhibitor complexes.

Malashkevich, V.N.Strop, P.Keller, J.W.Jansonius, J.N.Toney, M.D.

(1999) J Mol Biol 294: 193-200

  • DOI: https://doi.org/10.1006/jmbi.1999.3254
  • Primary Citation of Related Structures:  
    1D7R, 1D7S, 1D7U, 1D7V

  • PubMed Abstract: 

    The crystal structures of four inhibitor complexes of dialkylglycine decarboxylase are reported. The enzyme does not undergo a domain closure, as does aspartate aminotransferase, upon inhibitor binding. Two active-site conformations have been observed in previous structures that differ in alkali metal ion content, and two active-site conformations have been shown to coexist in solution when a single type of metal ion is present. There is no indication of coexisting conformers in the structures reported here or in the previously reported structures, and the observed conformation is that expected based on the presence of potassium in the enzyme. Thus, although two active-site conformations coexist in solution, a single conformation, corresponding to the more active enzyme, predominates in the crystal. The structure of 1-aminocyclopropane-1-carboxylate bound in the active site shows the aldimine double bond to the pyridoxal phosphate cofactor to be fully out of the plane of the coenzyme ring, whereas the Calpha-CO2(-) bond lies close to it. This provides an explanation for the observed lack of decarboxylation reactivity with this amino acid. The carboxylate groups of both 1-aminocyclopropane-1-carboxylate and 5'-phosphopyridoxyl-2-methylalanine interact with Ser215 and Arg406 as previously proposed. This demonstrates structurally that alternative binding modes, which constitute substrate inhibition, occur in the decarboxylation half-reaction. The structures of d and l-cycloserine bound to the active-site show that the l-isomer is deprotonated at C(alpha), presumably by Lys272, while the d-isomer is not. This difference explains the approximately 3000-fold greater potency of the l versus the d-isomer as a competitive inhibitor of dialkylglycine decarboxylase.


  • Organizational Affiliation

    Department of Structural Biology, Biozentrum University of Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland. malashkevich@wi.mit.edu


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
PROTEIN (2,2-DIALKYLGLYCINE DECARBOXYLASE (PYRUVATE))433Burkholderia cepaciaMutation(s): 0 
EC: 4.1.1.64
UniProt
Find proteins for P16932 (Burkholderia cepacia)
Explore P16932 
Go to UniProtKB:  P16932
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP16932
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NMA
Query on NMA

Download Ideal Coordinates CCD File 
D [auth A]N-[3-HYDROXY-2-METHYL-5-PHOSPHONOOXYMETHYL-PYRIDIN-4-YLMETHYL]-2-METHYLALANINE
C12 H19 N2 O7 P
NHGDGJKONAZETF-UHFFFAOYSA-N
K
Query on K

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

Download Ideal Coordinates CCD File 
B [auth A]SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Work: 0.185 
  • Space Group: P 64 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 153.2α = 90
b = 153.2β = 90
c = 86.9γ = 120
Software Package:
Software NamePurpose
AMoREphasing
TNTrefinement
MOSFLMdata reduction
CCP4data scaling
ROTAVATAdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1999-11-19
    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: 2017-10-04
    Changes: Refinement description
  • Version 1.4: 2023-08-09
    Changes: Data collection, Database references, Derived calculations, Refinement description