6H2P
Crystal Structure of Arg184Gln mutant of Human Prolidase with Mn ions and Cacodylate ligand
Summary for 6H2P
| Entry DOI | 10.2210/pdb6h2p/pdb |
| Related | 5mby 5mbz 5mc0 5mc1 5mc2 5mc3 5mc4 5mc5 |
| Descriptor | Xaa-Pro dipeptidase, MANGANESE (II) ION, CACODYLATE ION, ... (5 entities in total) |
| Functional Keywords | prolidase, peptidase, hydrolysis, pita-bread, metalloenzyme, mutation, hydrolase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 109984.00 |
| Authors | Wilk, P.,Piwowarczyk, R.,Weiss, M.S. (deposition date: 2018-07-14, release date: 2018-08-29, Last modification date: 2024-10-23) |
| Primary citation | Wilk, P.,Uehlein, M.,Piwowarczyk, R.,Dobbek, H.,Mueller, U.,Weiss, M.S. Structural basis for prolidase deficiency disease mechanisms. FEBS J., 285:3422-3441, 2018 Cited by PubMed Abstract: Prolidase is a metallopeptidase that cleaves iminodipeptides containing a proline (Pro) or hydroxyproline (Hyp) residue at their C-terminal end. The disease prolidase deficiency (PD) is a rare recessive human disorder characterized by reduced prolidase activity. PD manifests itself by a wide range of severe clinical symptoms, most commonly as skin ulceration, recurrent infections of the respiratory tract, and mental retardation. Several mutations in the PEPD gene have been identified that are responsible for the loss or the reduction of prolidase activity. In contrast, the structural basis of enzyme inactivation has so far remained elusive. In this study, we present high resolution crystal structures of a number of human prolidase (HsProl) variants, in which single amino acids are either substituted by others or deleted. The observed implications of the mutations on the three-dimensional structure of HsProl are reported and discussed and related to their enzymatic activity. The resulting structures may be divided into four groups depending on the presumed effect of the corresponding mutations on the reaction mechanism. The four possible inactivation mechanisms, which could be elucidated, are disruption of the catalytic Mn (OH )-center, introduction of chain disorder along with the displacement of important active site residues, rigidification of the active site, and flexibilization of the active site. PubMed: 30066404DOI: 10.1111/febs.14620 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.479 Å) |
Structure validation
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