1QIP: Human Glyoxalase I Complexed With S-P- Nitrobenzyloxycarbonylglutathione

Citation:
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.
PDB ID: 1QIPDownload
MMDB ID: 11507
PDB Deposition Date: 1999/6/14
Updated in MMDB: 1999/12
Experimental Method:
x-ray diffraction
Resolution: 1.72  Å
Source Organism:
Similar Structures:
Biological Unit for 1QIP: dimeric; determined by author and by software (PISA,PQS)
Molecular Components in 1QIP
Label Count Molecule
Proteins (2 molecules)
2
Protein (Lactoylglutathione Lyase)(Gene symbol: GLO1)
Molecule annotation
Chemicals (7 molecules)
1
2
2
3
3
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.