Back سربين Arabic Serpine German Serpina Spanish سرپین FA Serpine French Serpina GL סרפין HE Serpin ID Inibitore della serin proteasi Italian セルピン Japanese
| Serpin (serine protease inhibitor) | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
.png) A serpin (white) with its 'reactive centre loop' (blue) bound to a protease (grey). Once the protease attempts catalysis it will be irreversibly inhibited. (PDB: 1K9O) | |||||||||||
| Identifiers | |||||||||||
| Symbol | Serpin, SERPIN (root symbol of family) | ||||||||||
| Pfam | PF00079 | ||||||||||
| InterPro | IPR000215 | ||||||||||
| PROSITE | PDOC00256 | ||||||||||
| SCOP2 | 1hle / SCOPe / SUPFAM | ||||||||||
| CDD | cd00172 | ||||||||||
| |||||||||||
Serpins are a superfamily of proteins with similar structures that were first identified for their protease inhibition activity and are found in all kingdoms of life.[1][2] The acronym serpin was originally coined because the first serpins to be identified act on chymotrypsin-like serine proteases (serine protease inhibitors).[3][4][5] They are notable for their unusual mechanism of action, in which they irreversibly inhibit their target protease by undergoing a large conformational change to disrupt the target's active site.[6][7] This contrasts with the more common competitive mechanism for protease inhibitors that bind to and block access to the protease active site.[8][9]
Protease inhibition by serpins controls an array of biological processes, including coagulation and inflammation, and consequently these proteins are the target of medical research.[10] Their unique conformational change also makes them of interest to the structural biology and protein folding research communities.[7][8] The conformational-change mechanism confers certain advantages, but it also has drawbacks: serpins are vulnerable to mutations that can result in serpinopathies such as protein misfolding and the formation of inactive long-chain polymers.[11][12] Serpin polymerisation not only reduces the amount of active inhibitor, but also leads to accumulation of the polymers, causing cell death and organ failure.[10]
Although most serpins control proteolytic cascades, some proteins with a serpin structure are not enzyme inhibitors, but instead perform diverse functions such as storage (as in egg white—ovalbumin), transport as in hormone carriage proteins (thyroxine-binding globulin, cortisol-binding globulin) and molecular chaperoning (HSP47).[9] The term serpin is used to describe these members as well, despite their non-inhibitory function, since they are evolutionarily related.[1]
- ^ a b Cite error: The named reference
Silverman_2001was invoked but never defined (see the help page). - ^ Spence MA, Mortimer MD, Buckle AM, Minh BQ, Jackson CJ (June 2021). Echave J (ed.). "A Comprehensive Phylogenetic Analysis of the Serpin Superfamily". Molecular Biology and Evolution. 38 (7): 2915–2929. doi:10.1093/molbev/msab081. PMC 8233489. PMID 33744972.
- ^ Carrell RW, Boswell DR (1986). "Serpins: the superfamily of plasma serine proteinase inhibitors". In Barrett AJ, Salvesen G (eds.). Proteinase Inhibitors. Research monographs in cell and tissue physiology. Vol. 12. Amsterdam: Elsevier Science Publishers BV. pp. 403–420. ISBN 0-444-80763-2.
- ^ Silverman GA, Whisstock JC, Bottomley SP, Huntington JA, Kaiserman D, Luke CJ, Pak SC, Reichhart JM, Bird PI (August 2010). "Serpins flex their muscle: I. Putting the clamps on proteolysis in diverse biological systems". The Journal of Biological Chemistry. 285 (32): 24299–24305. doi:10.1074/jbc.R110.112771. PMC 2915665. PMID 20498369.
- ^ Whisstock JC, Silverman GA, Bird PI, Bottomley SP, Kaiserman D, Luke CJ, Pak SC, Reichhart JM, Huntington JA (August 2010). "Serpins flex their muscle: II. Structural insights into target peptidase recognition, polymerization, and transport functions". The Journal of Biological Chemistry. 285 (32): 24307–24312. doi:10.1074/jbc.R110.141408. PMC 2915666. PMID 20498368.
- ^ Huntington JA, Read RJ, Carrell RW (October 2000). "Structure of a serpin-protease complex shows inhibition by deformation". Nature. 407 (6806): 923–926. Bibcode:2000Natur.407..923H. doi:10.1038/35038119. PMID 11057674. S2CID 205009937.
- ^ a b Gettins PG (December 2002). "Serpin structure, mechanism, and function". Chemical Reviews. 102 (12): 4751–4804. doi:10.1021/cr010170. PMID 12475206.
- ^ a b Whisstock JC, Bottomley SP (December 2006). "Molecular gymnastics: serpin structure, folding and misfolding". Current Opinion in Structural Biology. 16 (6): 761–768. doi:10.1016/j.sbi.2006.10.005. PMID 17079131.
- ^ a b Cite error: The named reference
Law_2006was invoked but never defined (see the help page). - ^ a b Stein PE, Carrell RW (February 1995). "What do dysfunctional serpins tell us about molecular mobility and disease?". Nature Structural Biology. 2 (2): 96–113. doi:10.1038/nsb0295-96. PMID 7749926. S2CID 21223825.
- ^ Janciauskiene SM, Bals R, Koczulla R, Vogelmeier C, Köhnlein T, Welte T (August 2011). "The discovery of α1-antitrypsin and its role in health and disease". Respiratory Medicine. 105 (8): 1129–1139. doi:10.1016/j.rmed.2011.02.002. PMID 21367592.
- ^ Cite error: The named reference
Carrell_1997was invoked but never defined (see the help page).