1QIP

HUMAN GLYOXALASE I COMPLEXED WITH S-P-NITROBENZYLOXYCARBONYLGLUTATHIONE


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.72 Å
  • R-Value Free: 0.210 
  • R-Value Work: 0.180 
  • R-Value Observed: 0.170 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Reaction mechanism of glyoxalase I explored by an X-ray crystallographic analysis of the human enzyme in complex with a transition state analogue.

Cameron, A.D.Ridderstrom, M.Olin, B.Kavarana, M.J.Creighton, D.J.Mannervik, B.

(1999) Biochemistry 38: 13480-13490

  • DOI: https://doi.org/10.1021/bi990696c
  • Primary Citation of Related Structures:  
    1QIN, 1QIP

  • PubMed Abstract: 

    The structures of human glyoxalase I in complexes with S-(N-hydroxy-N-p-iodophenylcarbamoyl)glutathione (HIPC-GSH) and S-p-nitrobenzyloxycarbonylglutathione (NBC-GSH) have been determined at 2.0 and 1.72 A resolution, respectively. HIPC-GSH is a transition state analogue mimicking the enediolate intermediate that forms along the reaction pathway of glyoxalase I. In the structure, the hydroxycarbamoyl function is directly coordinated to the active site zinc ion. In contrast, the equivalent group in the NBC-GSH complex is approximately 6 A from the metal in a conformation that may resemble the product complex with S-D-lactoylglutathione. In this complex, two water molecules occupy the liganding positions at the zinc ion occupied by the hydroxycarbamoyl function in the enediolate analogue complex. Coordination of the transition state analogue to the metal enables a loop to close down over the active site, relative to its position in the product-like structure, allowing the glycine residue of the glutathione moiety to hydrogen bond with the protein. The structure of the complex with the enediolate analogue supports an "inner sphere mechanism" in which the GSH-methylglyoxal thiohemiacetal substrate is converted to product via a cis-enediolate intermediate. The zinc ion is envisioned to play an electrophilic role in catalysis by directly coordinating this intermediate. In addition, the carboxyl of Glu 172 is proposed to be displaced from the inner coordination sphere of the metal ion during substrate binding, thus allowing this group to facilitate proton transfer between the adjacent carbon atoms of the substrate. This proposal is supported by the observation that in the complex with the enediolate analogue the carboxyl group of Glu 172 is 3.3 A from the metal and is in an ideal position for reprotonation of the transition state intermediate. In contrast, Glu 172 is directly coordinated to the zinc ion in the complexes with S-benzylglutathione and with NBC-GSH.


  • Organizational Affiliation

    Department of Molecular Biology, Uppsala University, Biomedical Center, Sweden. [email protected]


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
PROTEIN (LACTOYLGLUTATHIONE LYASE)
A, B, C, D
183Homo sapiensMutation(s): 1 
EC: 4.4.1.5
UniProt & NIH Common Fund Data Resources
Find proteins for Q04760 (Homo sapiens)
Explore Q04760 
Go to UniProtKB:  Q04760
PHAROS:  Q04760
GTEx:  ENSG00000124767 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ04760
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
GNB
Query on GNB

Download Ideal Coordinates CCD File 
F [auth A],
I [auth B],
L [auth C],
O [auth D]
S-P-NITROBENZYLOXYCARBONYLGLUTATHIONE
C18 H24 N4 O10 S
QYFGPQQSJQOGEO-TVJRNMROSA-N
BME
Query on BME

Download Ideal Coordinates CCD File 
G [auth A],
J [auth B],
M [auth C],
P [auth D]
BETA-MERCAPTOETHANOL
C2 H6 O S
DGVVWUTYPXICAM-UHFFFAOYSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
E [auth A],
H [auth B],
K [auth C],
N [auth D]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.72 Å
  • R-Value Free: 0.210 
  • R-Value Work: 0.180 
  • R-Value Observed: 0.170 
  • Space Group: P 43
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 67.3α = 90
b = 67.3β = 90
c = 167.7γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1999-11-24
    Type: Initial release
  • Version 1.1: 2007-10-16
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Derived calculations, Version format compliance
  • Version 1.3: 2023-12-27
    Changes: Data collection, Database references, Derived calculations