{{Infobox protein family | Symbol = Pacifastin_I | Name = Pacifastin_I | image = PDB 1kio EBI.jpg | width = | caption = solution structure of the small serine protease inhibitor sgci[l30r, k31m] | Pfam = PF05375 | Pfam_clan = | InterPro = IPR008037 | SMART = | PROSITE = | MEROPS = | SCOP = 1kgm | TCDB = | OPM family = | OPM protein = | CAZy = | CDD = }} '''Pacifastin''' is a family of [[serine]] [[Protease inhibitor (biology)|proteinase inhibitors]] found in [[arthropods]].<ref name="pmid14705960">{{cite journal| vauthors=Rawlings ND, Tolle DP, Barrett AJ| title=Evolutionary families of peptidase inhibitors. | journal=Biochem J | year= 2004 | volume= 378 | issue= Pt 3 | pages= 705–16 | pmid=14705960 | doi=10.1042/BJ20031825 | pmc=1224039 }}</ref><ref name="pmid18775459">{{cite journal| vauthors=Breugelmans B, Simonet G, van Hoef V, Van Soest S, Vanden Broeck J| title=Pacifastin-related peptides: structural and functional characteristics of a family of serine peptidase inhibitors. | journal=Peptides | year= 2009 | volume= 30 | issue= 3 | pages= 622–32 | pmid=18775459 | doi=10.1016/j.peptides.2008.07.026 | s2cid=8797134 }}</ref> Pacifastin [[Inhibitor protein|inhibits]] the serine [[peptidase]]s [[trypsin]] and [[chymotrypsin]].<ref name="pmid15147757">{{cite journal |vauthors=Parkinson NM, Conyers C, Keen J, MacNicoll A, Smith I, Audsley N, etal | title=Towards a comprehensive view of the primary structure of venom proteins from the parasitoid wasp Pimpla hypochondriaca. | journal=Insect Biochem Mol Biol | year= 2004 | volume= 34 | issue= 6 | pages= 565–71 | doi=10.1016/j.ibmb.2004.03.003 | pmid=15147757 | bibcode=2004IBMB...34..565P }}</ref>

All pacifastin members that have been [[Biological classification|characterized]] at the [[molecule|molecular]] level are [[Protein precursor|precursor]] [[peptides]] composed of an [[N-terminus#Signal peptide|N-terminal signal sequence]] followed by a precursor domain and a variable number of [[Inhibitor protein|inhibitor]] [[Protein domain|domain]]s. Each of these inhibitor domains carries a six-cysteine motif – see below.

The first family members to be identified were isolated from ''Locusta migratoria migratoria'' ([[migratory locust]]) which were HI, LMCI-1 (PMP-D2) and LMCI-2 (PMP-C).<ref name="pmid1472051">{{cite journal | vauthors = Boigegrain RA, Mattras H, Brehélin M, Paroutaud P, Coletti-Previero MA | title = Insect immunity: two proteinase inhibitors from hemolymph of Locusta migratoria | journal = Biochem. Biophys. Res. Commun. | volume = 189 | issue = 2 | pages = 790–3 | date=December 1992 | pmid = 1472051 | doi = 10.1016/0006-291x(92)92271-x}}</ref><ref name="pmid1740125">{{cite journal | vauthors = Nakakura N, Hietter H, Van Dorsselaer A, Luu B | title = Isolation and structural determination of three peptides from the insect Locusta migratoria. Identification of a deoxyhexose-linked peptide | journal = Eur. J. Biochem. | volume = 204 | issue = 1 | pages = 147–53 | date=February 1992 | pmid = 1740125 | doi = 10.1111/j.1432-1033.1992.tb16617.x| doi-access = }}</ref><ref name="pmid10696590">{{cite journal | vauthors = Boigegrain RA, Pugnière M, Paroutaud P, Castro B, Brehélin M | title = Low molecular weight serine protease inhibitors from insects are proteins with highly conserved sequences | journal = Insect Biochem. Mol. Biol. | volume = 30 | issue = 2 | pages = 145–52 | date=February 2000 | pmid = 10696590 | doi = 10.1016/s0965-1748(99)00109-5| bibcode = 2000IBMB...30..145B }}</ref> A further five members, SGPI-1 to 5, were then isolated from ''Schistocerca gregaria'' ([[desert locust]]),<ref name="pmid9475173">{{cite journal | vauthors = Hamdaoui A, Wataleb S, Devreese B, Chiou SJ, Vanden Broeck J, Van Beeumen J, De Loof A, Schoofs L | title = Purification and characterization of a group of five novel peptide serine protease inhibitors from ovaries of the desert locust, Schistocerca gregaria | journal = FEBS Lett. | volume = 422 | issue = 1 | pages = 74–8 | date=January 1998 | pmid = 9475173 | doi = 10.1016/s0014-5793(97)01585-8| s2cid = 35980008 | doi-access = | bibcode = 1998FEBSL.422...74H }}</ref><ref name="pmid11856311">{{cite journal | vauthors = Gáspári Z, Patthy A, Gráf L, Perczel A | title = Comparative structure analysis of proteinase inhibitors from the desert locust, Schistocerca gregaria | journal = Eur. J. Biochem. | volume = 269 | issue = 2 | pages = 527–37 | date=January 2002 | pmid = 11856311 | doi = 10.1046/j.0014-2956.2001.02685.x | doi-access = free }}</ref> and a [[protein dimer|heterodimeric]] [[serine protease]] inhibitor was isolated from the haemolymph of ''Pacifastacus leniusculus'' ([[Signal crayfish]]), and named pacifastin.<ref name="pmid9192625">{{cite journal | vauthors = Liang Z, Sottrup-Jensen L, Aspán A, Hall M, Söderhäll K | title = Pacifastin, a novel 155-kDa heterodimeric proteinase inhibitor containing a unique transferrin chain | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 94 | issue = 13 | pages = 6682–7 | date=June 1997 | pmid = 9192625 | pmc = 21218 | doi = 10.1073/pnas.94.13.6682| bibcode = 1997PNAS...94.6682L | doi-access = free }}</ref>

==Function== [[Peptide]] proteinase inhibitors are in many cases [[Protein biosynthesis|synthesised]] as part of a larger [[Protein precursor|precursor]] protein, referred to as a [[Prepropeptide|propeptide]] or [[zymogen]], which remains inactive until the precursor domain is cleaved off in the [[lysosome]], the precursor domain preventing access of the [[Enzyme substrate|substrate]] to the [[active site]] until necessary. Proteinase inhibitors destined for secretion have an additional N-terminal signal-peptide domain which will be cleaved by a signal-peptidase. Removal of these one or two N-terminal inhibitor domains, either by interaction with a second peptidase or by [[autocatalytic]] [[Bond cleavage|cleavage]], will activate the zymogen.<ref name="pmid15147757"/>

Very little is known about the [[endogenous]] function of pacifastin-like inhibitors except that they may play roles in arthropod [[Immunity (medical)|immunity]] and in regulation of the [[Physiology|physiological]] processes involved in [[insect]] [[reproduction]].<ref name="pmid22154999">{{cite journal| vauthors=Wang S, Cui Z, Liu Y, Li Q, Song C | title=The first homolog of pacifastin-related precursor in the swimming crab (Portunus trituberculatus): characterization and potential role in immune response to bacteria and fungi. | journal=Fish Shellfish Immunol | year= 2012 | volume= 32 | issue= 2 | pages= 331–8 | pmid=22154999 | doi=10.1016/j.fsi.2011.11.025 | bibcode=2012FSI....32..331W }}</ref>

==Structure==

The inhibitor unit of pacifastin is a [[Protein motif|conserved pattern]] of six [[cysteine]] residues (Cys1 – Xaa9–12 – Cys2 – Asn – Xaa – Cys3 – Xaa – Cys4 – Xaa2–3 – Gly – Xaa3–6 – Cys5 – Thr – Xaa3 – Cys6). Detailed analysis of the 3-D structure shows that these six residues form three [[disulfide bridge]]s (Cys1–4, Cys2–6, Cys3–5), giving members of the pacifastin family a typical fold and remarkable stability.<ref name="pmid19364530">{{cite journal| vauthors=Breugelmans B, Simonet G, van Hoef V, Van Soest S, Smagghe G, Vanden Broeck J| title=A lepidopteran pacifastin member: cloning, gene structure, recombinant production, transcript profiling and in vitro activity. | journal=Insect Biochem Mol Biol | year= 2009 | volume= 39 | issue= 7 | pages= 430–9 | doi=10.1016/j.ibmb.2009.03.005 | pmid=19364530 | bibcode=2009IBMB...39..430B }}</ref>

Pacifastin is a 155[[Dalton (unit)|kDa]] [[protein]] composed of two [[covalently]] linked subunits, which are separately encoded. The heavy [[polymer|chain]] of pacifastin (105 kDa) is related to [[transferrins]] as it carries three [[transferrin]] lobes, two of which seem to be active in [[iron]] [[Binding (molecular)|binding]].<ref name="pmid9192625"/> A number of the transferrin family members are also serine peptidases, and belong to MEROPS peptidase family S60 ([https://www.ebi.ac.uk/interpro/IEntry?ac=IPR001156 INTERPRO]). The light chain of pacifastin (44 kDa) is the proteinase inhibitory subunit, and consists of up to nine cysteine-rich inhibitory [[protein domains|domains]] that are [[Homology (biology)|homologous]] to each other. The locust inhibitors share a [[conserved sequence|conserved]] array of six [[cysteine|residues]] with the pacifastin light chain. The [[secondary structure|structure]] of members of this family reveals that they consist of a triple-stranded [[Antiparallel (biochemistry)|antiparallel]] [[beta-sheet]] connected by three disulphide bridges.<ref name="pmid9192625"/>

This family of [[serine]] [[protease inhibitor (biology)|protease inhibitor]]s belongs to MEROPS inhibitor family I19, clan IW. They [[Enzyme inhibitor|inhibit]] [[chymotrypsin]], a peptidase belong to the S1 family ([https://www.ebi.ac.uk/interpro/IEntry?ac=IPR001254 INTERPRO]).<ref name="pmid14705960"/>

==References== {{reflist}} {{InterPro content|IPR008037}}

[[Category:Protein families]]