周秀菊,刘党生,蒋宇扬
ZHOU Xiu ju 1, LIU Dang sheng 1, JIAGN Yu yang 2 (1.School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China; 2.The Key Laboratory of Bioorganic Phosphorus Chemistry, Ministry of Education; Department of C

• 1:沈阳药科大学制药工程学院
• 2:沈阳药科大学制药工程学院
• 3:清华大学生命有机磷化学教育部重点实验室 辽宁沈阳110016
• 4:辽宁沈阳110016

摘要(Abstract)：

目的综述肌酸激酶的结构与功能研究进展以及应用。方法根据近年来的文献 ,介绍了肌酸激酶的结构、在不同条件下伴随构象变化其功能的改变机制、生理功能的研究进展以及实际应用。结果肌酸激酶是研究蛋白质体内折叠的机制的理想模型 ,已经取得了突破性的进展 ,为生物大分子的结构与功能理论提供了依据。肌酸激酶具有重要的生理功能 ,目前在临床如肿瘤检测方面已有广泛的应用。结论对肌酸激酶的结构与功能的研究 ,将会广泛地应用于临床诊断、新药研究等方面。
Objective This article reviewed the progress in application of creatine kinase and the relationship between the structure and functions. Methods The structure and the relationship between its activation and conformation changes under different conditions were mainly introduced according to the documents in recent years. Here we also reviewed the advance of studies on its physiological roles and its application. Results CK is an ideal model for studying the unfolding and refolding of protein in vitro . The mechanisms of folding will be helpful to understanding the theory of the relationship between the structure and function of high molecules. In addition to its physiological role, CK is important in the diagnoses of some diseases such as clinical tumor specimens. Conclusions It will be widely used on clinical diagnoses and discoveries of new drugs depending on the study of the relationship between its structure and functions.

关键词(KeyWords)： 肌酸激酶;构象;变性;复性
creatine kinase; conformation; denaturation; renaturation

Abstract:

Keywords:

基金项目(Foundation):

作者(Authors): 周秀菊,刘党生,蒋宇扬
ZHOU Xiu ju 1, LIU Dang sheng 1, JIAGN Yu yang 2 (1.School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China; 2.The Key Laboratory of Bioorganic Phosphorus Chemistry, Ministry of Education; Department of C

参考文献(References)：

• [1]KubyS,NoltmanE .Creatinekinase[J].TheEnzymes,1962,6:515-6030.
• [2]AlanC ,Mclaughin.Theinteractionof8 anilino1 naph thalen esulfonatewithcreatinekinase[J].TheJournalofBiologicalChemistry,1974,249(5):1445-1452.
• [3]WillianE ,Jacobus,AlbertLL .Creatinekinaseofratheartmitochondria[J].TheJournalofBiologicalChemistry,1973,248(13):4803-4810.
• [4]TheoWallimann,MalusWyss,DieterBrdicaka.Intracellu larcomparemen tion,structureandfunctionofcreatineki nase:isoenzymesintissueswithhighandfluctuatingener gydemands:thephosphocreatinecircuit’forcellularener gyhomeostasis[J].BiochemJ,1992,281(1):21-40.
• [5]EricMTowler,LoriKWilson,YuChunZhou,etal.AcompletesystemforidentifyinginhibitorsofcreatinekinaseB [J].AnalyticalBiochemistry,2000,279(1):96-99.
• [6]ScottPutney,WalterHerlihy,NancyRoyal.Rabbitmusclecreatinephosphokinase[J].Communication,1984,259(23):14317-14320.
• [7]CharlesPordahl,GregoryLevans,ThomasA ,etal.CompletC DNAderivedaminoacidseque nceofchickmusclecre atinekinase[J].TheJournalofBiologicalChemistry,1984(24):15224-15227.
• [8]WattsDC .Creatinekinase[J].TheEnzyme,1974,8:383-455.
• [9]MohanaRaoJK ,GrzegrzBujacz.Crystalstructureofrabbitmusclecreatinekinase[J].FEBSLetters1998,439(1):133-137.
• [10]KarinFritz wolf,ThomasSchnyder,TheoWallimann,etal.Structuerofmitochondrialcreatinekinase[J].LettersToNature,1996,381(23):341-345.
• [11]CookPF ,KenyonGL ,ClelandWW ,etal.UseofpHstud iestoelucidatethecatalyticmechanismofrabbitmusclecreatinekinase[J].Biochemistry,1981,20(4):1204-1210.
• [12]BorderCLJr,RiordanJF .Essentialarginylresiduesinre versetranscriptase[J].Biochemistry,1975,14:4699-4704.
• [13]LinLijun,PerrymanMB ,FriedmanDzvid,etal.Determi nationofthecatalyticsiteofcreatinekinasebysitedirect edmutagenesis[J].BiochemicaetBiophysicaActa,1994,1206(1):97-104.
• [14]MichaelCOlcott,MaryL ,Bradley,etal.Photoaffinityla belingofcreatinekinasewith2 azido and8 azidoadenosinetriphosphate:IdentificationoftwopeptidesfromtheATP bind ingdomain[J].Biochemistry,1994,33(39):11935-11941.
• [15]ZhouHaiMeng,ZhangXiaoHong,YongYin,etal.Con formationalchangesattheactivesiteofcreatinekinaseatlowconcentrationsofguanidiniumchloride[J].BiochemJ,1993,291(1):103-107.
• [16]TsouChenLu.Locationoftheactivesitesofsomeenzymesinlimitedandflexiblemolecularregions[J].TrendsinBiochemicalSciences,1986,11(10):427-429.
• [17]姚启智,周海梦,侯立向,等,肌酸激酶在胍溶液中的变性与失活速度的比较[J].中国科学B辑,1982,(12):1084-1088.
• [18]ZhouHaiMeng,TsouChenLu.Comparisonofactivityandconformationchangesduringrefoldingofurea denaturedcreatinekinase[J].BiochimicaetBophysicaActa,1986,869(1):69-74.
• [19]邹晓明,侯立向,陈显川.肌酸激酶在SDS溶液中失活与构象变化的比较研究[J].生物化学与生物物理学报,1992,24(6):559-567.
• [20]TimothyWebb,PhilipJJacson,GlinnEMorris.Proteasedigestionstudiesofanequilibriumintermediateintheun foldingofcreatinekinase[J].BiochemJ,1997,321(1):83-88.
• [21]GlennEMorris,AlisonJCartwright.Monoclonalantibodystudiessuggestacatalytidsiteattheinterfacebetweendo mainsincreatinekinase[J].BiochimicaetBiophysicaAc ta,1990,1039,(3):318-322.
• [22]YangHP ,ZhongHN ,ZhouHM ,etal.Catalysisofthere foldingofureadenaturedcreatinekinasebypeptidyl prolyscis transisomerase.BiophyActa,1997,1338(2):147-150.
• [23]ParkYD ,ZhouHM .EffectofMg2+ duringreactivationandrefoldingfuanidine.Hydrochloridedenaturedcreatineki nase[J].JProteinChemistry,2000,19(2):193-198.
• [24]OkanoK ,YamaiotoK ,OhbaY ,etal.Determinationofcreatinekinaseisozymeinseraandtissuesofpatientswithvariouslungcarcinomas[J].ClinChemActa,1987,10(3):147-164.
• [25]成继民,陈兴,张哲.线粒体肌酸激酶在肺癌组织中的表达[J].中国肿瘤临床,2000,27(1):12-13.
• [26]张淇哲,王晓玲,张敬一,等.106例肺癌组织中线粒体肌酸激酶免疫组化的研究[J].中国肿瘤临床与康复,1997,4(3):4.
• [27]成继民,陈兴,张乃哲.线粒体肌酸激酶在乳腺肿瘤的表达及意义[J].现代诊断与治疗,1997,8(1):10-11.
• [28]YukioIshiguro,KanefusaKatoMD .ThediagnosticandprognosticvalueofpretreatmentserumcreatinekinaseBBlevelsinpatientswithneuroblastoma[J].Cancer,1990,65:2014-2019.
• [29]JaffeAS.Diagnosticchangesinplasmacreatinekinaseiso formsearlyaftertheonsetofacutemyocardialinfarction.Circulation,1986,74-105.
• [30]秦勤,崔让庄,赵炳让,等.血清肌钙蛋白和肌酸激酶MB同工酶质量在诊断急性心肌梗塞中的应用[J].中国循环杂志,2000,15(5):279.
• [31]王伟,王颜刚,王宝华.糖尿病患者血清肌酸激酶活性变化的临床意义[J].山东医药,1997,37(12):11-12.