4AW6
Crystal structure of the human nuclear membrane zinc metalloprotease ZMPSTE24 (FACE1)
Summary for 4AW6
| Entry DOI | 10.2210/pdb4aw6/pdb |
| Descriptor | CAAX PRENYL PROTEASE 1 HOMOLOG, ZINC ION, 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE (3 entities in total) |
| Functional Keywords | hydrolase, m48 peptidase, integral membrane protein, prelamin a processing, ageing, progeria |
| Biological source | HOMO SAPIENS (HUMAN) |
| Cellular location | Endoplasmic reticulum membrane ; Multi-pass membrane protein : O75844 |
| Total number of polymer chains | 4 |
| Total formula weight | 226248.25 |
| Authors | Pike, A.C.W.,Dong, Y.Y.,Quigley, A.,Dong, L.,Cooper, C.D.O.,Chaikuad, A.,Goubin, S.,Shrestha, L.,Li, Q.,Mukhopadhyay, S.,Yang, J.,Xia, X.,Shintre, C.A.,Barr, A.J.,Berridge, G.,Chalk, R.,Bray, J.E.,von Delft, F.,Bullock, A.,Bountra, C.,Arrowsmith, C.H.,Edwards, A.,Burgess-Brown, N.,Carpenter, E.P. (deposition date: 2012-05-31, release date: 2012-07-25, Last modification date: 2024-05-08) |
| Primary citation | Quigley, A.,Dong, Y.Y.,Pike, A.C.W.,Dong, L.,Shrestha, L.,Berridge, G.,Stansfeld, P.J.,Sansom, M.S.P.,Edwards, A.M.,Bountra, C.,von Delft, F.,Bullock, A.N.,Burgess-Brown, N.A.,Carpenter, E.P. The Structural Basis of Zmpste24-Dependent Laminopathies. Science, 339:1604-, 2013 Cited by PubMed Abstract: Mutations in the nuclear membrane zinc metalloprotease ZMPSTE24 lead to diseases of lamin processing (laminopathies), such as the premature aging disease progeria and metabolic disorders. ZMPSTE24 processes prelamin A, a component of the nuclear lamina intermediate filaments, by cleaving it at two sites. Failure of this processing results in accumulation of farnesylated, membrane-associated prelamin A. The 3.4 angstrom crystal structure of human ZMPSTE24 has a seven transmembrane α-helical barrel structure, surrounding a large, water-filled, intramembrane chamber, capped by a zinc metalloprotease domain with the catalytic site facing into the chamber. The 3.8 angstrom structure of a complex with a CSIM tetrapeptide showed that the mode of binding of the substrate resembles that of an insect metalloprotease inhibitor in thermolysin. Laminopathy-associated mutations predicted to reduce ZMPSTE24 activity map to the zinc metalloprotease peptide-binding site and to the bottom of the chamber. PubMed: 23539603DOI: 10.1126/SCIENCE.1231513 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.4 Å) |
Structure validation
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