4OGF

Crystal Structure of Human DJ-1 with glyoxylate as substrate analog

Summary for 4OGF

• Entry DOI: 10.2210/pdb4ogf/pdb
• Related: 4OFW 4OGG
• Descriptor: Protein DJ-1 (2 entities in total)
• Functional Keywords: glyoxalase, lyase
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane; Lipid-anchor: Q99497
• Total number of polymer chains: 1
• Total formula weight: 19744.81

Authors

Choi, D.,Kim, J.,Ryu, K.-S.,Park, C. (deposition date: 2014-01-16, release date: 2014-10-15, Last modification date: 2023-09-20)

Primary citation

Choi, D.,Kim, J.,Ha, S.,Kwon, K.,Kim, E.H.,Lee, H.Y.,Ryu, K.S.,Park, C.
Stereospecific mechanism of DJ-1 glyoxalases inferred from their hemithioacetal-containing crystal structures.
Febs J., 281:5447-5462, 2014

PubMed Abstract: DJ-1 family proteins have recently been characterized as novel glyoxalases, although their cofactor-free catalytic mechanisms are not fully understood. Here, we obtained crystals of Arabidopsis thaliana DJ-1d (atDJ-1d) and Homo sapiens DJ-1 (hDJ-1) covalently bound to glyoxylate, an analog of methylglyoxal, forming a hemithioacetal that presumably mimics an intermediate structure in catalysis of methylglyoxal to lactate. The deuteration level of lactate supported the proton transfer mechanism in the enzyme reaction. Differences in the enantiomeric specificity of d/l-lactacte formation observed for the DJ-1 superfamily proteins are explained by the presence of a His residue in the active site with essential Cys and Glu residues. The model for the stereospecificity was further evaluated by a molecular modeling simulation with methylglyoxal hemithioacetal superimposed on the glyoxylate hemithioacetal. The mechanism of DJ-1 glyoxalase provides a basis for understanding the His residue-based stereospecificity.

PubMed: 25283443
DOI: 10.1111/febs.13085

Experimental method

X-RAY DIFFRACTION (1.6 Å)