9CSJ
Crystal structure of human glyoxalase domain-containing protein 4 (GLOD4) at 2.33 A resolution.
Summary for 9CSJ
| Entry DOI | 10.2210/pdb9csj/pdb |
| Descriptor | Isoform 2 of Glyoxalase domain-containing protein 4, MAGNESIUM ION, ZINC ION, ... (7 entities in total) |
| Functional Keywords | glyoxalase domain-containing protein 4, metallo-b-lactamase synuclein nitrase, metal binding protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 3 |
| Total formula weight | 101602.78 |
| Authors | Griswold-Prenner, I.,Dou, Y.,Jennings, A.,Kayser, F. (deposition date: 2024-07-24, release date: 2025-08-13, Last modification date: 2026-02-25) |
| Primary citation | Wright, S.,Dang, V.C.,Hussain, S.,Kandel, P.,Brendza, R.P.,Mazhar, S.,Whitmore, M.,Boudoukha, S.,Kaur Banwait, J.,Van Der Linden, R.,Vertudes, E.,Markham, K.,Trzeciak, M.,Pohan, G.,Jennings, A.,Shahidi-Latham, S.,Kayser, F.,Beckstead, M.,Lucius, A.L.,Kashyap, A.,Ischiropoulos, H.,Griswold-Prenner, I. Selective peroxynitrite-mediated protein nitration catalyzed by glyoxalase domain containing protein 4. Proc.Natl.Acad.Sci.USA, 123:e2515002123-e2515002123, 2026 Cited by PubMed Abstract: Tyrosine nitration alters the structure, function, and cellular localization of proteins and is implicated in the pathology of multiple diseases [G. Ferrer-Sueta , , 1338-1408 (2018), H. Ischiropoulos, , 1-11 (1998), I. Griswold-Prenner , , 105038-10554 (2023)]. Although protein nitration is assumed to proceed via nonspecific chemical mechanisms, it is highly selective, suggesting the possibility of enzymatic catalysis. Here, we showed that glyoxalase domain-containing protein 4 (GLOD4), a previously uncharacterized protein, is an enzyme that catalyzes selective protein nitration. A primary in vivo target for GLOD4-mediated nitration is alpha-synuclein (α-syn), which is central to the pathogenesis of Parkinson's disease (PD) and related disorders. We document tyrosine nitration of α-syn by GLOD4 in vitro, in cells, and in a murine model of synuclein pathology. The data identified a function of GLOD4 and other structurally related proteins that catalyze the peroxynitrite-mediated selective protein tyrosine nitration. This enzymatic catalysis of nitration may unearth pathophysiological mechanisms and potential interventions in diseases such as PD, cancer, and autoimmunity. PubMed: 41628334DOI: 10.1073/pnas.2515002123 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.33 Å) |
Structure validation
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