Background
VaspinisanewlydescribedADIpocytokineexpressedpredominantlyinvisceralwhiteadiposetissues.StructureanalysisofVaspinpredictsthepresenceofthreeβ-sheets,nineα-helices,andonecentralloop,whicharedistinctivestructuralfeaturesofSerpinfamilymembers.TheserpinsareirreversIBLe(“suicidal”)serine-proteaseinhibitors,characterizedbyhavingmorethan30%sequencehomologywithα1-antitrypsinandaconservedtertiarystructure,whichcontainsanexposedreactivecenterloopthatactsasapseudo-substrateforthetargetproteinase.MembersofthisfamilyplayanimportantroleinanumberoffundamentalBIOLOGicalprocessesincludingbloodcoagulation,fibrinolysis,complementactivation,angiogenesis,inflammation,andtumorsuppression.Inhuman,theserpinsrepresentapproximately2%oftotalserumproteins,ofwhich70%isα1-antitrypsin.Vaspinexhibits40.2%sequenceidentitywithα-1-antitrypsin.Yet,itsproteaseinhibitoryactivityisstillunknown.VaspinmRNAexpressioninvisceralfatispositivelycorrelatedwithBMIandpercentofbodyfat.AdmiNISTrationofVaspintoobesemiceimprovedglucosetoleranceandinsulinsensitivity,reflectedbynormalizedbloodglucoselevels.Italsoledtothereversalofalteredexpressionofdiabetes-relevantadipocytokinesincludingleptin,adiponectin,resistin,andTNF-α.ThesefindingssuggestapotentialclinicaluseforVaspininamelioratingcertainaberrationsseeninthediabetic/obesitymetabolicsyndrome.RecombinanthumanVaspinisa45.2kDaproteincontaining395amino-acidresidues.
Specifications