1S4B
Crystal structure of human thimet oligopeptidase.
Summary for 1S4B
| Entry DOI | 10.2210/pdb1s4b/pdb |
| Descriptor | Thimet oligopeptidase, ZINC ION (3 entities in total) |
| Functional Keywords | zinc metallopeptidase domain, hydrolase |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasm: P52888 |
| Total number of polymer chains | 1 |
| Total formula weight | 77575.37 |
| Authors | Ray, K.,Hines, C.S.,Coll-Rodriguez, J.,Rodgers, D.W. (deposition date: 2004-01-15, release date: 2004-07-20, Last modification date: 2024-02-14) |
| Primary citation | Ray, K.,Hines, C.S.,Coll-Rodriguez, J.,Rodgers, D.W. Crystal structure of human thimet oligopeptidase provides insight into substrate recognition, regulation, and localization J.Biol.Chem., 279:20480-20489, 2004 Cited by PubMed Abstract: Thimet oligopeptidase (TOP) is a zinc metallopeptidase that metabolizes a number of bioactive peptides and degrades peptides released by the proteasome, limiting antigenic presentation by MHC class I molecules. We present the crystal structure of human TOP at 2.0-A resolution. The active site is located at the base of a deep channel that runs the length of the elongated molecule, an overall fold first seen in the closely related metallopeptidase neurolysin. Comparison of the two related structures indicates hinge-like flexibility and identifies elements near one end of the channel that adopt different conformations. Relatively few of the sequence differences between TOP and neurolysin map to the proposed substrate-binding site, and four of these variable residues may account for differences in substrate specificity. In addition, a loop segment (residues 599-611) in TOP differs in conformation and degree of order from the corresponding neurolysin loop, suggesting it may also play a role in activity differences. Cysteines thought to mediate covalent oligomerization of rat TOP, which can inactivate the enzyme, are found to be surface-accessible in the human enzyme, and additional cysteines (residues 321,350, and 644) may also mediate multimerization in the human homolog. Disorder in the N terminus of TOP indicates it may be involved in subcellular localization, but a potential nuclear import element is found to be part of a helix and, therefore, unlikely to be involved in transport. A large acidic patch on the surface could potentially mediate a protein-protein interaction, possibly through formation of a covalent linkage. PubMed: 14998993DOI: 10.1074/jbc.M400795200 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
Download full validation report
