Transglutaminases: Multiple Functional Modifiers and Targets for New Drug Discovery PDF
Preview Transglutaminases: Multiple Functional Modifiers and Targets for New Drug Discovery
Kiyotaka Hitomi · Soichi Kojima Laszlo Fesus E ditors Transglutaminases Multiple Functional Modifi ers and Targets for New Drug Discovery Transglutaminases . Kiyotaka Hitomi (cid:129) Soichi Kojima (cid:129) Laszlo Fesus Editors Transglutaminases Multiple Functional Modifiers and Targets for New Drug Discovery Editors KiyotakaHitomi SoichiKojima GraduateSchoolofPharmaceutical Micro-SignalingRegulationTechnologyUnit Sciences RIKENCenterforLifeScience NagoyaUniversity Technologies(CLST) Nagoya,Japan Wako,Saitama,Japan LaszloFesus RIKENMolecularandChemicalSomatology DepartmentofBiochemistryand TokyoMedicalandDentalUniversity MolecularBiology Bunkyo-ku,Tokyo,Japan UniversityofDebrecen Debrecen,Hungary ISBN978-4-431-55823-1 ISBN978-4-431-55825-5 (eBook) DOI10.1007/978-4-431-55825-5 LibraryofCongressControlNumber:2015958519 SpringerTokyoHeidelbergNewYorkDordrechtLondon ©SpringerJapan2015 Thisworkissubjecttocopyright.AllrightsarereservedbythePublisher,whetherthewholeorpartof the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilarmethodologynowknownorhereafterdeveloped. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publicationdoesnotimply,evenintheabsenceofaspecificstatement,thatsuchnamesareexempt fromtherelevantprotectivelawsandregulationsandthereforefreeforgeneraluse. Thepublisher,theauthorsandtheeditorsaresafetoassumethattheadviceandinformationinthis book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained hereinorforanyerrorsoromissionsthatmayhavebeenmade. Printedonacid-freepaper SpringerJapanKKispartofSpringerScience+BusinessMedia(www.springer.com) Preface Posttranslational modification, which refers to covalent and generally enzymatic modificationofproteinsduringorafterproteinbiosynthesis,isahighlyimportant subject ofthenext-generation,post-genome research.Among various posttransla- tionalmodifications,enzymesthatcatalyzeprotein–proteincross-linkingreactions aretransglutaminasesconservedfrommicroorganismstomammals,formingcova- lentisopeptide bondsbetweenpeptide-boundglutamineandlysine residuesunder strictregulatoryconditions.Transglutaminasesalsocatalyzeattachmentofprimary amine (transamidation) or replacement to glutamic acid residue (deamidation) at theglutamineresidues.Inmammals,thisenzymefamilyconsistsofeightisoforms (isozymes)differentiallyexpressedinvarioustissues. Althoughthefirstdescriptionontransglutaminasewasmadealmost60yearsago andnumerousstudieshavebeenperformedtocharacterizetheseenzymesandtheir physiological and pathological roles, there are many unresolved issues. Newer and newermysterieshaveevolved,andoncetheanswerstothesearefound,thechallenge ofapplicationofnovelknowledgetopracticaluseremainsforthefuture.Intriguing transglutaminasefeaturesincludediversefunctionsandsometimesopposingactivi- ties of transglutaminase family members, their multiple and changing localization insideandoutsideofcells,theirnon-enzymaticinteractionsandscaffoldingactivity, themechanismoftheirsecretion,andsoon.Bytransglutaminase-catalyzedreactions thestructure,function,andstabilityofthesubstrateproteinsarealtered,associating withanumberofbiologicalphenomena.Theuniquecatalyticreactionsandmultiple interactionsoftransglutaminaseshavefascinatedmanyscientistsduringthelastsix decades sothat they have achieved biological significance in a wide scientific area andapplicationsinchemical,food,cosmetic,andpharmaceuticalindustries.Because the aberrant activity or ectopic expression of the enzymes causes several diseases, inhibitory and regulatory molecules have been developed as promising new drugs. Additionally, the dramatic advances in molecular life science technologies have broughtmuchprogressinallthetransglutaminaseresearchareas. Consideringcurrenttrendsandadvances,weplannedtopublishthisreviewbook tocoverbasicknowledgeandnovelfindingsintransglutaminaseresearch.Wehave v vi Preface attempted to review structures, expression, functions, and regulatory mechanisms from the scope of enzymology, biochemistry, physiology, pathology, pharmacol- ogy, chemistry, and applied bioscience. Particularly, we focused on diseases and drugdevelopmentrelatedtotheenzymes’roleinvariouspathologies. At the Gordon Research Conference on Transglutaminases in Human Disease Processes held in Italy in 2014, we discussed with the authors, who have been engagedinprominenttransglutaminasework,thepurposeandscopeofthebook’s contentanddecidedtodevotemorespacetobasicknowledgeunderlyingthetheme ofeachchapter,inadditiontothenew,cutting-edgefindings,sothat“newcomers” can obtain useful information and technical insight, and most importantly an interestinstudyingtheseenigmaticenzymesinthefuture. The book could not have been achieved without the full dedication of each contributingauthorandthepeoplewhohavesupportedus.Wehopethatitwilldevelop afurtherbasisofnewcollaborationsbystabilizing“cross-linking”ofresearchersand newcomersinthefuture. Nagoya,Japan KiyotakaHitomi Wako,Japan SoichiKojima Debrecen,Hungary LaszloFesus Contents 1 StructureofTransglutaminases:UniqueFeaturesServeDiverse Functions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Ma´te´ A´.Deme´ny,IlmaKorponay-Szab(cid:1)o,andLa´szl(cid:1)oFe´su¨s 2 ControlofTGFunctionsDependingonTheirLocalization. . . . . . 43 YutakaFurutaniandSoichiKojima 3 PreferredSubstrateStructureofTransglutaminases. . . . . . . . . . . 63 KiyotakaHitomiandHidekiTatsukawa 4 InsightsintoTransglutaminase2FunctionGained fromGeneticallyModifiedAnimalModels. . . . . . . . . . . . . . . . . . . 83 SiiriE.Iismaa 5 TransglutaminaseinInvertebrates. . . . . . . . . . . . . . . . . . . . . . . . . 117 ToshioShibataandShun-ichiroKawabata 6 ANewIntegrin-BindingSiteonaTransglutaminase-Catalyzed Polymer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129 YasuyukiYokosaki 7 Transglutaminase2-MediatedGeneRegulation. . . . . . . . . . . . . . . 153 Soo-YoulKim 8 TheRoleofTransglutaminaseType2intheRegulation ofAutophagy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171 ManuelaD’Eletto,FedericaRossin,MariaGraziaFarrace, andMauroPiacentini 9 Transglutaminase2andCeliacDisease.. . . . .. . . . .. . . . .. . . . .. 193 RasmusIversenandLudvigM.Sollid 10 TransglutaminaseIIandMetastasis:HowHotIstheLink?. . . . . . 215 KapilMehta vii viii Contents 11 Transglutaminases:ExpressioninKidneyandRelationtoKidney Fibrosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229 ElisabettaA.M.Verderio,GiuliaFurini,IzharW.Burhan, andTimothyS.Johnson 12 TransglutaminasesinBoneFormationandBoneMatrix Stabilization. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 263 CuiCuiandMariT.Kaartinen 13 TransglutaminasesandNeurologicalDiseases. . . . . . . . . . . . . . . . 283 JulianneFeola,AlinaMonteagudo,LauraYunes-Medina, andGailV.W.Johnson 14 RegulationofTransglutaminase2byOxidativeStress. . . . . . . . . . 315 EuiManJeongandIn-GyuKim 15 BloodCoagulationFactorXIII:AMultifunctional Transglutaminase. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 333 MoyuruHayashiandKohjiKasahara 16 InhibitionofTransglutaminase. . . . . . . . . . . . . . . . . . . . . . . . . . . . 347 JeffreyW.Keillor 17 SubstrateEngineeringofMicrobialTransglutaminase forSite-SpecificProteinModificationandBioconjugation. . . . . . . 373 NorihoKamiyaandYutaroMori Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 385 Chapter 1 Structure of Transglutaminases: Unique Features Serve Diverse Functions Ma´te´ A´.Deme´ny,IlmaKorponay-Szab(cid:1)o,andLa´szl(cid:1)oFe´su¨s Abstract Understanding the diverse functions and pathologies of transglu- taminases requires detailed analysis and interpretation of their structures. This chapter is an attempt to describe in detail how these enzymes are folded into functional domains, what type of catalytic and scaffolding functions have been gained as the result of their evolution, how their regulation is achieved through unique Ca2+ and purine nucleotide binding sites, redox changes and specific proteolytic actions, and by influencing the equilibrium of open-close configura- tions.Theimportanceofstructuralmotifsinpathologiesisunderlinedbytheceliac epitopesoftransglutaminase2,responsibleforautoimmunereactions. Keywords Domain organization • Crystallography • Catalytic mechanism • Regulation • Ca2+ • Purine nucleotides • Proteolysis • Redox • Open-close conformation•Substrates•Interactions•Celiacepitope 1.1 Introduction Transglutaminases(Tgases)arealargefamilyofenzymescanonicallyresponsible for amidation of protein and non-protein amines. They are ubiquitous in higher organisms but have also been identified in lower life forms, including archea, bacteria, plants, worms and insects. Their structural core and catalytic residues are strongly related to proteases and other hydrolases. Their common ancestor evolved to utilize acyl acceptors other than water by changing the active site so that it would be less accessible for water by a mechanism that is perfected in the vertebrate enzymes. The simple ancient Tgases, similar to the present microbial enzymes, acquired additional domains to serve regulatory, interacting and new enzymatic functions. In some instances these additions rendered them zymogens, whichshowdifferentialactivitybasedonproteolyticactivation.Theyevolvedtobe M.A´.Deme´ny•L.Fe´su¨s(*) DepartmentofBiochemistryandMolecularBiology,UniversityofDebrecen,Debrecen, Hungary e-mail:[email protected] I.Korponay-Szab(cid:1)o DepartmentofPediatrics,UniversityofDebrecen,Debrecen,Hungary ©SpringerJapan2015 1 K.Hitomietal.(eds.),Transglutaminases,DOI10.1007/978-4-431-55825-5_1
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