7OBM
Crystal structure of the human Prolyl Endopeptidase-Like protein short form (residues 90-727)
Summary for 7OBM
| Entry DOI | 10.2210/pdb7obm/pdb |
| Descriptor | Prolyl endopeptidase-like (1 entity in total) |
| Functional Keywords | esterase mitochondrial beta-propeller, structural genomics, psi-2, protein structure initiative, mitochondrial protein partnership, mpp, hydrolase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 73575.57 |
| Authors | Rosier, K.,McDevitt, M.T.,Brendan, J.F.,Marcaida, M.J.,Bingman, C.A.,Pagliarini, D.J.,Creemers, J.W.M.,Smith, R.W.,Mitochondrial Protein Partnership (MPP) (deposition date: 2021-04-22, release date: 2021-11-10, Last modification date: 2024-06-19) |
| Primary citation | Rosier, K.,McDevitt, M.T.,Smet, J.,Floyd, B.J.,Verschoore, M.,Marcaida, M.J.,Bingman, C.A.,Lemmens, I.,Dal Peraro, M.,Tavernier, J.,Cravatt, B.F.,Gounko, N.V.,Vints, K.,Monnens, Y.,Bhalla, K.,Aerts, L.,Rashan, E.H.,Vanlander, A.V.,Van Coster, R.,Regal, L.,Pagliarini, D.J.,Creemers, J.W.M. Prolyl endopeptidase-like is a (thio)esterase involved in mitochondrial respiratory chain function. Iscience, 24:103460-103460, 2021 Cited by PubMed Abstract: Deficiency of the serine hydrolase prolyl endopeptidase-like (PREPL) causes a recessive metabolic disorder characterized by neonatal hypotonia, feeding difficulties, and growth hormone deficiency. The pathophysiology of PREPL deficiency and the physiological substrates of PREPL remain largely unknown. In this study, we connect PREPL with mitochondrial gene expression and oxidative phosphorylation by analyzing its protein interactors. We demonstrate that the long PREPL isoform localizes to mitochondria, whereas PREPL remains cytosolic. KO mice showed reduced mitochondrial complex activities and disrupted mitochondrial gene expression. Furthermore, mitochondrial ultrastructure was abnormal in a PREPL-deficient patient and KO mice. In addition, we reveal that PREPL has (thio)esterase activity and inhibition of PREPL by Palmostatin M suggests a depalmitoylating function. We subsequently determined the crystal structure of PREPL, thereby providing insight into the mechanism of action. Taken together, PREPL is a (thio)esterase rather than a peptidase and PREPL is involved in mitochondrial homeostasis. PubMed: 34888501DOI: 10.1016/j.isci.2021.103460 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.1 Å) |
Structure validation
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