4JUE
Crystal structure of Plasmodium falciparum ubiquitin conjugating enzyme UBC9
Summary for 4JUE
| Entry DOI | 10.2210/pdb4jue/pdb |
| Related | 4M1N |
| Descriptor | Ubiquitin conjugating enzyme UBC9 (2 entities in total) |
| Functional Keywords | sumo, e2 enzyme, protein binding |
| Biological source | Plasmodium falciparum |
| Total number of polymer chains | 4 |
| Total formula weight | 73440.20 |
| Authors | Reiter, K.H.,Boucher, L.E.,Bosch, J.,Matunis, J.M. (deposition date: 2013-03-24, release date: 2013-08-21, Last modification date: 2024-04-03) |
| Primary citation | Reiter, K.,Mukhopadhyay, D.,Zhang, H.,Boucher, L.E.,Kumar, N.,Bosch, J.,Matunis, M.J. Identification of Biochemically Distinct Properties of the Small Ubiquitin-related Modifier (SUMO) Conjugation Pathway in Plasmodium falciparum. J.Biol.Chem., 288:27724-27736, 2013 Cited by PubMed Abstract: Small ubiquitin-related modifiers (SUMOs) are post-translationally conjugated to other proteins and are thereby essential regulators of a wide range of cellular processes. Sumoylation, and enzymes of the sumoylation pathway, are conserved in the malaria causing parasite, Plasmodium falciparum. However, the specific functions of sumoylation in P. falciparum, and the degree of functional conservation between enzymes of the human and P. falciparum sumoylation pathways, have not been characterized. Here, we demonstrate that sumoylation levels peak during midstages of the intra-erythrocyte developmental cycle, concomitant with hemoglobin consumption and elevated oxidative stress. In vitro studies revealed that P. falciparum E1- and E2-conjugating enzymes interact effectively to recognize and modify RanGAP1, a model mammalian SUMO substrate. However, in heterologous reactions, P. falciparum E1 and E2 enzymes failed to interact with cognate human E2 and E1 partners, respectively, to modify RanGAP1. Structural analysis, binding studies, and functional assays revealed divergent amino acid residues within the E1-E2 binding interface that define organism-specific enzyme interactions. Our studies identify sumoylation as a potentially important regulator of oxidative stress response during the P. falciparum intra-erythrocyte developmental cycle, and define E1 and E2 interactions as a promising target for development of parasite-specific inhibitors of sumoylation and parasite replication. PubMed: 23943616DOI: 10.1074/jbc.M113.498410 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.851 Å) |
Structure validation
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