5類有毒動物毒液金屬蛋白酶研究進展

徐志文，任雪敏，吳朝妍，雷 林

5類有毒動物毒液金屬蛋白酶研究進展

徐志文1，任雪敏2*，吳朝妍3，雷 林1

（1. 遵義市林業局，貴州 遵義 563000；2. 遵義市林業科學研究所，貴州 遵義 563000；3. 西南林業大學 云南省森林災害預警與重點實驗室，云南 昆明 650224）

金屬蛋白酶普遍存在于動物、植物及細菌等生物體中。金屬蛋白酶被保留在蛇、蝎子、寄生蜂、水母及蜘蛛的毒液中，參與生理學過程，在其捕食、防御及消化等過程中發揮著重要作用。文章歸納了金屬蛋白酶家族分類，截至目前分為17組74個家族，闡述了這5類攜毒動物毒液金屬蛋白酶在序列結構、家族分類、生物活性、功能機制等方面的研究，發現M10家族金屬蛋白酶存在于寄生蜂和水母毒液中，M13家族金屬蛋白酶存在于寄生蜂和蝎子毒液中，M12家族金屬蛋白酶普遍存在于蛇、寄生蜂、蝎子、水母毒液中。蛇毒液金屬蛋白酶研究相對深入和全面，其具有降解細胞外基質蛋白、調控細胞、抑制血小板聚集等活性及功能。在蝎子、寄生蜂、蜘蛛及水母中的毒液金屬蛋白酶研究相對較少，其分子結構、功能及作用機制等尚不明晰。本研究將加深學者對毒液金屬蛋白酶的認識，并為毒液金屬蛋白酶今后的研究方向和應用提供參考。

毒液金屬蛋白酶；家族分類；生物活性；功能機制；研究

金屬蛋白酶是生物體內行使功能的主要蛋白酶成分之一，在動植物及微生物的發育調控、免疫應答及非生物逆境脅迫響應等生理學過程中發揮著重要作用。金屬蛋白酶是包含金屬小肽和大分子金屬蛋白的一類蛋白酶，其活性主要是依賴一種或多種金屬離子，是能夠催化肽類和蛋白質中肽鍵水解的一類蛋白酶。在蛇、蜘蛛、蝎子、寄生蜂及水母這5類攜毒動物的毒液或毒素中也保守存在，有趣的是金屬蛋白酶作為這5類攜毒動物毒液或毒素蛋白的主要組成成分[1-6]，在其捕食及消化等過程中發揮重要作用。本文從金屬蛋白酶的結構及家族分類，其在蛇、蝎子、寄生蜂、蜘蛛及水母5類動物毒液中的研究進展進行綜述，為后期毒液金屬蛋白酶研究方向和應用提供參考。

1 金屬蛋白酶的結構及家族分類

根據酶的催化位點類型將金屬蛋白酶劃分為32個家族（M1-M33，未見M21），一半的家族含有與金屬離子捆綁的“His-Glu-Xaa-Xaa-His”（或者“HEXXH”）五肽結構，另一半家族的金屬離子不與五肽結構捆綁[7]。該五肽“HEXXH”的共識序列能被更精確的定義為“abXHEbbHbc”，其中b是不帶電荷的殘基、c是疏水性的殘基、X幾乎可以是任何氨基酸[8]。32個家族的金屬蛋白酶被分為5個超家族，第一超家族（gluzincin, MA）含有捆綁金屬離子的“HEXXH+E”形式的催化結構域，該組別含有M1（membrane alanyl）、M2（peptidyl-dipeptidase）、M4（thermolysin）、M5（mycolysin）和M13（neprilysin）共5個家族。第二超家族（metzincin, MB）含有捆綁金屬離子的“HEXXH+H”形式的催化結構域，該組別含有M12（astacin，包括astacin和reprolysin亞家族）、M10（interstitial collagenase，包括serralysin和matrixin亞家族）、M11（Autolysin）和M7（streptomyces small neutral protease）共4個家族。第三超家族（other metallopeptidase with “HEXXH” motif）含有捆綁未知金屬離子“HEXXH+E”形式的催化結構域，該組別含有M3（thimet oligopeptidase）、M6（immune inhibitor A）、M8（leishmanolysin）、M9（vibrio collagenase）、M26（IgA-specific metalloendopeptidase）、M27（tetanus toxin）、M30（staphylococcus neutral protease）、M31（clostridial collagenase）、M32（carboxypeptidase Taq）等9個家族。第四超家族（other metallopeptidases with known metal ligands）是所捆綁金屬離子結合在“HEXXH”以外的區域，該組別含有M14（carboxypeptidase A）、M15（zinc D-Ala-D-Ala carboxypeptidase）、M16（pitrilysin）、M17（leucyl aminopeptidase）、M24（methionyl aminopeptidase）等5個家族。第五超家族（metallopeptidases with unknown metal ligands）捆綁的金屬離子配體、氨基酸及位置是完全未知的，該組別含有M18（yeast aminopeptidase I）、M19（membrane dipeptidase）、M20（glutamate carboxypeptidase）、M22（O-Sialoglycoprotein endopeptidase）、M23（β-lytic endopeptidase）、M25（X-His-dipeptidase）、M28（vibrio leucyl aminopeptidase）、M29（thermophilic aminopeptidase）、M33（aminopeptidase Y）等9個家族[7]。Rawling等[9]基于一級結構和序列同源性將所有金屬蛋白酶分為MA、MC、MD和ME等17個組，17個組細化為M1、M2和M3等74個家族組成，但該分類未見用于毒液金屬蛋白酶的研究。

基于金屬蛋白酶的家族分類情況，研究者可將蛇、蜘蛛、蝎子、寄生蜂及水母5類攜毒動物毒液中發現的金屬蛋白酶進行分類。蛇、蝎子、蜘蛛及寄生蜂中普遍發現的毒液金屬蛋白酶屬于Metzincin（MB）組中的M12家族[10-12]，少數幾種蝎子和寄生蜂毒液金屬蛋白酶屬于Gluzincin（MA）組中的M13家族[1]，極少數寄生蜂毒液金屬蛋白酶屬于M10家族[13]，水母刺細胞中發現M10和M12家族的毒液金屬蛋白酶[14]。

2 5類攜毒動物毒液金屬蛋白酶

2.1 蛇毒液金屬蛋白酶

金屬蛋白酶廣泛存在于蛇毒液中，其單一序列結構、酶活特性及功能等在蛇毒液研究中較為深入。它們屬于MA組中的M12家族，Reprolysin成員。蛇毒液中的金屬蛋白酶（snake venom metalloproteinases, SVMPs）根據其功能活性、核酸序列及結構域可分為4類：P-I型，只含有1個金屬蛋白酶結構域（metalloproteinase domain，M）；P-II型，含有P-I型的金屬蛋白酶結構域和一個去整合素結構域（disintegrin domain，D）；P-III型，包含3個結構域，在P-II型基礎上再加一個富半胱氨酸結構域（cysteine-rich domain，C）；P-IV型，在P-III型的基礎上，其富含半胱氨酸結構域末端再連接捆綁有二硫鍵的凝集素樣結構域（lectin-like domains）[10,15]。但在2008年，有研究[16]以蛇毒液金屬蛋白酶的mRNA序列和蛋白質結構為依據，重新將P-IV型SVMPs歸為P-III型。目前，SVMPs主要分為3個類型：P-I型（Ia）、P-II型（IIa、IIb、IIc、IId）、P-III型（IIIa、IIIb、IIIc、IIId）[17]。P-I型、P-II型和P-III型的分子量大小不一，P-I型的分子量一般介于20～30 kDa，P-II型的分子量范圍一般為30～60 ku，P-III型的分子量一般介于60～100 ku[2]，但僅以分子量大小來判斷其家族歸屬類型是不準確的。

SVMPs可降解細胞外基質蛋白（extracellular matrix proteins，ECM），溶解基底膜中的膠原蛋白（collagen）、彈性蛋白（elastin）、層粘連蛋白（laminin）、明膠（gelatin）、纖維連接蛋白（fibronectin）、纖維蛋白原（fibrinogen）、巢蛋白（內功素，nidogen）和凝血酶敏感蛋白（thrombospondin）等組成成分[18-21]，對纖維蛋白原的降解能力最強。SVMPs可降解纖維蛋白原的α鏈和β鏈[22]，其中P-I SVMPs對α鏈水解性強[17,19]，P-II和P-III SVMPs對α和β鏈都具有較強水解活性[18]。蛇毒液金屬蛋白酶具有溶纖維原、催化凝血酶原、激活凝血因子X、調控細胞、抑制血小板聚集、促發炎、滅活絲氨酸蛋白酶抑制劑等活性及功能[2,23-31]，使咬傷的動物體出現內部凝血系統受損、血栓形成、細胞凋亡、血管壞死等發生，外部出現組織受損、炎癥、水腫及出血等現象[20,32-34]。蛇毒液金屬蛋白酶注入動物體最直接且肉眼可見的影響是導致出血和水腫[10,35]，絕大部分的P-II SVMPs和P-III SVMPs具強烈的出血活性，也有非出血性和促凝血的P-II和P-III SVMPs，如Berythractivase、Ecarin和HV1等[17,36-37]。對于Fibrolase、、Atroxase、ACLF和r ACLF等[38-41]絕大部分P-I SVMPs僅有蛋白水解活性，未曾展現出血效應或低出血效應，少部分P-I SVMPs具出血效應[42]。血小板聚集是作用于止血的復雜機制，SVMPs可以結合并切割血小板受體GPIbα和GPVI、血漿vWF受體，進一步溶解纖維蛋白原使血小板纖維原蛋白粘附受阻，從而影響血小板凝集功能[19,43-47]。

在探究蛇毒液金屬蛋白酶功能時，發現SVMPs不僅可溶解血栓還可作用于癌細胞，有望開發成溶血栓劑和抗癌藥物。SVMPs的溶纖維蛋白活性會影響血小板凝聚功能，抑制止血和血栓形成，因此可考慮作為溶血栓的潛在藥物[19,45,47-48]。一種P-I SVMP rACLF能誘導宮頸癌細胞（hela cells）形態改變、分離和活性降低，但具體的機理還不清楚[38]。P-II SVMPs可能對腫瘤的轉移有治療潛力，這個過程需要細胞外基質與整聯蛋白相互作用。有研究表明：P-II SVMPs可以阻止依賴RGD（arginine-glycine-aspartic acid，RGD）的αIIbβ3、α5β1、αVβ1、αVβ3等整聯蛋白受體，參與腫瘤細胞的遷移和侵襲[49-50]。由于P-III SVMPs能裂解vWF，所以正在被開發成抗癌藥物，如：Bothropoidin、Kaouthiagin、Jararhagin和Leucurogin等。含有93個氨基酸的Leucurogin對黑色素瘤細胞黏著、遷移、增值、轉移、生長具有一定作用[51]；49 ku的P-IIIa SVMP Bothropoidin可誘導使細胞凋亡、遷移、粘附，抑制乳腺癌細胞和血管增生[52]；52 ku的P-IIIb SVMP Jararhagin可誘導細胞增加caspase-3通路，最終消減體內的腫瘤結節[33]。SVMPs作用于癌細胞的機制，可能是其包含的金屬蛋白酶結構、去整合素結構和富含半胱氨酸去整合素結構能裂解ECM蛋白所致，而ECM蛋白決定著細胞的粘附等功能。

2.2 蝎子毒液金屬蛋白酶

蝎子對人類生命健康造成嚴重威脅，非洲、中東、南美等熱帶地區每年有大量人被蝎子蜇傷，甚至致死。蝎子毒液由水、鹽、脂質、毒素、氨基酸、多糖、核苷酸、多肽、蛋白質和其它未知化合物組成，蛋白質、肽酶、神經毒素是蝎毒毒性主要作用成分[6,53-55]。蝎子毒液中的透明質酸酶、絲氨酸蛋白酶、金屬蛋白酶等酶，參與毒液注射并發揮重要作用[56-57]。金屬蛋白酶作為主要成分被保留于蝎子毒液蛋白中，這些蛋白酶需要一個二價金屬離子作為輔基，而具有蛋白水解活性[2,58]。最早，Fletcher等[59]在毒液中分離出一種命名為Antarease的純化物可能是金屬蛋白酶，對囊泡膜蛋白有裂解活性。目前，有研究揭示了、和等蝎子的毒液能夠裂解強啡肽1-13（dynorphin 1-13），這種降解活性可能與金屬蛋白酶有關[60-61]?？蓡我恍佣疽航饘俚鞍酌傅乃饣钚?、功能及機制等仍不明晰[58,62-63]。

至2014年，研究者揭示了蝎子毒液水解纖維蛋白原的確與金屬蛋白酶相關，且分析了分離純化得到的金屬蛋白酶的裂解位點[1]。值得注意的是，Carmo等[1]發現的毒液金屬蛋白酶（TsMs1-9）與蛇、蜘蛛毒液金屬蛋白酶同屬于Metzincin超家族中的M12家族，而TsMs10與其家族分類不同，歸類于Gluzincin超家族中的M13家族。也有研究者純化鑒定到了一種與高血壓相關的類血管緊張素轉換酶（angiotensin-converting enzyme-like peptidase，ACE），該蛋白酶與金屬蛋白酶具有較高的同源性[64]，屬于M13家族。近些年，相繼在、、和等蝎子[6,56,65-69]毒液中發現大量金屬蛋白酶，僅有少部分研究通過直接純化或蛋白表達來探索單一蝎子毒液金屬蛋白酶的生物活性及功能[70]，現今關于蝎子毒液金屬蛋白酶的生物活性、家族分類及功能機制等研究停滯不前，需填補很多空白來揭示和了解金屬蛋白酶在蝎子毒液中扮演的角色。

2.3 蜘蛛毒液金屬蛋白酶

有關蜘蛛毒液蛋白報道涉及平甲蛛屬、狡蛛屬、洞葉蛛屬和寇蛛屬等屬，但平甲蛛屬在世界上分布最廣且造成咬傷衛生事件最多[71]。對平甲蛛屬毒液蛋白研究也相對較早和較深入，在20世紀70和80年代就有研究者通過免疫組化技術、組織化學技術、凝膠電泳和分離等生物技術方法，在和等平甲蛛屬蜘蛛毒液中發現存在蛋白酶[72-75]。首次發現蜘蛛毒液金屬蛋白酶是在平甲蛛屬的毒液中，被命名為Loxolysin A和Loxolysin B，Loxolysin A是一種能降解纖維連接蛋白和纖維蛋白原Aα和Bβ鏈、分子量為20～28 kDa的金屬蛋白酶，Loxolysin B是一種具有降解明膠活性、分子量為32～35 kDa的金屬蛋白酶[76]。隨之，在、和等蜘蛛[77]毒液中相繼發現金屬蛋白酶存在，這些蜘蛛毒液金屬蛋白酶具有水解膠原蛋白、纖維連接蛋白和纖維蛋白原等胞外基質蛋白的活性。但都未得到金屬蛋白酶序列，且其表達特征、功能和家族歸屬一直未被論證。直到2007年，首次從毒液腺體的cDNA文庫中鑒別出了一個類蝦紅素金屬蛋白酶（astacin-like metalloprotease）序列，被定名為擁有Astacin家族標簽的LALP[11]。類蝦紅素蛋白酶是Metzincin超家族M12家族中的成員，它有18個氨基酸形成催化結構域“–HEXXHXXGXX HEXXRXDR–”，其中3個組氨酸與鋅結合的共識序列是必要的催化活性中心，金屬活性位點含保守的甲硫氨酸殘基被稱為甲硫氨酸變區（MXY）[78-80]。Astacin家族成員被發現在多種生物體中，擁有多樣而獨特的生物學功能，在成熟生物體或胚胎的特定組織中表達[78,81-82]。而在動物毒液中存在未見有報道，研究首次揭示金屬蛋白酶作為Astacin家族成員存在于蜘蛛毒液中，且LALP能夠水解纖維蛋白和纖維連接蛋白，對兔內皮細胞有毒性[11]。但也有學者從蜘蛛毒液中鑒定出一種命名為Partitagin的金屬蛋白酶，未闡述其所屬家族，但有降解胞外基質活性和抑制血小板凝集功能[83-84]。

多個被命名為LALPs的蝦紅素樣蛋白酶在平甲蛛屬蜘蛛毒液中被鑒定到，其多種異構體在蜘蛛毒液中形成一個種內和種間毒素家族[85-87]。并且Astacins在和等蜘蛛毒液中高表達，表明蝦紅素樣金屬蛋白酶在平甲蛛屬蜘蛛毒液中具有重要的生物學意義[85,87-89]。有研究發現，在平甲蛛屬蜘蛛毒液中鑒定到的蝦紅素樣金屬蛋白酶具有降解胞外基質活性、溶纖維蛋白原、抑制血小板凝集等活性功能[71,86,90-91]。這些研究結果證實，在平甲蛛屬蜘蛛毒液中被保守共有的M12家族類蝦紅素金屬蛋白酶參與毒液注入生物體，發揮調節其他分子或直接參與捕獵、促進取食等重要功能[92]。

2.4 寄生蜂毒液金屬蛋白酶

大量文獻通過轉錄組和蛋白組等生物技術對蝶蛹金小蜂、管氏腫腿蜂、菜蛾盤絨繭蜂、頸雙緣姬蜂、椰心葉甲嚙小蜂等[93-97]寄生蜂毒液組成進行了分析，發現金屬蛋白酶在其毒液器官中作為主要成分存在。研究者通過系統發育樹和數據庫Blast比對發現，寄生蜂毒液中存在的金屬蛋白酶屬于M10、M12和M13家族，被保守共有的絕大部分毒液金屬蛋白酶屬于M12家族，少部分為M13家族，M10家族極少[13]。目前，在綠長背泥蜂、阿爾蚜繭蜂、隆脊匙胸癭蜂、波氏匙胸癭蜂、短背繭蜂屬、短背繭蜂屬、椰心葉甲嚙小蜂和管氏腫腿蜂等幾種毒液中發現M13家族金屬蛋白酶[93,98-101]，僅在中紅側溝繭蜂毒液中發現一個M10家族金屬蛋白酶[13]，這兩個家族的寄生蜂毒液金屬蛋白酶活性、功能及機制都尚不明晰。

寄生蜂毒液中的M12家族金屬蛋白酶被較早發現且普遍存在，但也僅有少部分研究揭示了其活性結構，在水解活性及功能機制等方面的研究仍匱乏。例如，寮黑瘤姬蜂毒液中分子量為39.9 kDa的Reprolysin金屬蛋白酶，含有2個與鋅結合的組氨酸殘基保守催化結構域為HELGHVFSAPRD。由于其可能有特異性底物，普通底物不能檢測到它的活性[102-103]。蜾蠃巨柄姬小蜂和櫛角姬小蜂毒液金屬蛋白酶的催化結構域為HELGHLLNxxHD[12]，麗蠅蛹集金小蜂毒液中的金屬蛋白酶活性催化位點為HELGHNLGxxHD[104]，且Formesyn等[105]發現麗蠅蛹集金小蜂毒液金屬蛋白酶對寄主細胞活性有影響。另外，在櫛角姬小蜂毒液中發現3個金屬蛋白酶基因（、、）編碼的氨基酸序列與麗蠅蛹集金小蜂、蜾蠃巨柄姬小蜂和寮黑瘤姬蜂毒液金屬蛋白酶氨基酸序列的相似性極高，且櫛角姬小蜂毒液金屬蛋白酶能阻礙寄主番茄葉蛾的生長發育[12]。之后很長一段時間未見有報道寄生蜂毒液金屬蛋白酶蛋白活性及功能機制研究，最新的是Lin等[13]在中紅側溝繭蜂毒液中發現了一種調控寄主細胞包囊的金屬蛋白酶，并闡釋清楚該毒液金屬蛋白酶是通過TOLL通路來行使功能的分子機制。以上這些報道的M12家族金屬蛋白酶，在序列結構上與蛇毒液金屬蛋白酶保守序列的同源性較高，其催化位點結構域的氨基酸殘基組成都為“HEXGHXXGXXHD”形式。

2.5 水母毒素金屬蛋白酶

水母類刺胞動物在捕獵和防御過程中，主要通過刺細胞內包含的大量毒素蛋白行使功能。但由于水母類刺胞動物的毒液難以收集，致使其毒液成分的研究相對其他攜毒動物要滯后。在、、、、白色霞水母、、、沙海蜇、海蜇、等大量水母的研究報道中，發現金屬蛋白酶在毒素提取物中占主要成分且發揮重要毒力作用[106-109]。其中沙海蜇中的毒液成分及毒液金屬蛋白酶被研究的最多，發現其毒液中存在M10家族的基質金屬蛋白酶和M12家族的類蝦紅素金屬蛋白酶[14]。有研究者在沙海蜇中發現至少存在9個分子量為28～46 ku、57～83 ku和139 ku間的毒液金屬蛋白酶[107]，且影響多種炎癥因子表達增強炎癥[110]。2021年，有研究者首次報道了沙海蜇毒液金屬蛋白酶可直接降解基底膜成分來增加血管的通透性導致水腫[111]，其與毒素成分中的調節因子有協同效應，在調節亞基的激活下可水解偶氮酪蛋白，且首次在水母毒液中獲得了3個與金屬蛋白酶相關的多肽序列[112]。近期，有研究者發現沙海蜇毒液金屬蛋白酶，與促使肌肉明顯腫脹、增加血清中肌酸激酶（CK）和乳酸脫氫酶（LDH）含量、刺激肌肉組織炎癥、破壞肌肉組織結構等相關[113]。以上都是通過粗毒液分離純化的方法獲得金屬蛋白酶提取物，未通過序列的表達純化獲得單一的毒液金屬蛋白酶。雖然水母毒液提取物中檢測到金屬蛋白酶存在，但它仍然是一類尚不清楚的金屬蛋白酶。由于水母毒素量小、成分復雜且不穩定等原因，很難從水母毒液中純化提取到單一的金屬蛋白酶及完整序列，這限制了對其分子結構、家族分類、功能及作用機制等的研究。

3 小結與展望

本文概述了當前金屬蛋白酶的家族分類，目前最新分為17組74個家族，但關于毒液金屬蛋白酶家族研究普遍應用的是5個超家族32個家族的分類。毒液金屬蛋白酶作為攜毒動物中一類重要的水解酶，在蛇、蝎子、寄生蜂、水母及蜘蛛毒液中都發現存在大量金屬蛋白酶，研究者對其序列結構、家族分類、生物活性、功能機制等的研究深度不一。通過對這5類攜毒動物毒液金屬蛋白酶家族歸類的研究進行總結，發現M10家族金屬蛋白酶存在于寄生蜂和水母毒液中，M13家族金屬蛋白酶存在于寄生蜂和蝎子毒液中，M12家族金屬蛋白酶普遍存在于蛇、寄生蜂、蝎子、水母毒液中。在蛇毒液中的金屬蛋白酶活性、生物功能、家族歸類及機制探究較為深入，具降解細胞外基質蛋白、催化凝血酶原、調控細胞、抑制血小板聚集、促發炎等活性及功能，且已經有不少種類的蛇毒液金屬蛋白酶被應用到抗血栓、血清解毒、抗癌等醫藥領域。而在蝎子、寄生蜂、水母及蜘蛛4類動物毒液中的研究相對較少，特別是基于單一毒液金屬蛋白酶核酸序列的研究。它在這4類動物毒液中扮演的角色引人思考，具體結構特征、活性功能和作用機制等亟待科研工作者深入探究?；跉w納的毒液金屬蛋白酶在5類攜毒動物中的研究現狀，結合高通量測序、基因克隆、重組表達及蛋白互作等生物技術手段，將為毒液金屬蛋白酶的研究及應用開拓思路。隨著攜毒動物毒液金屬蛋白酶活性、功能及作用機理的不斷挖掘，將在消炎、解毒、溶血栓、滅殺癌細胞等人類醫藥方面貢獻重要作用。

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Research Progress on Venom Metalloproteinases of Five Types of Poison-carrying Animals

XU Zhiwen1, REN Xuemin2*, WU Chaoyan3, LEI Lin1

（1. Forestry Bureau of Zunyi, Zunyi, Guizhou 563000, China; 2. Zunyi Institute of Forestry Sciences, Zunyi, Guizhou 563000, China; 3. Key Laboratory of Forest Disaster Warning and Control of Yunnan Province, Southwest Forestry University, Kunming 650224, China）

Metalloproteinases are commonly found in organisms such as animals, plants and bacteria, and it is worth noting that metalloproteinases are retained in the venom of snakes, scorpions, parasitic wasps, jellyfishes, and spider, and participate in physiological processes, and play important roles in their predation, defense and digestion. This paper summarized the classification of metalloprotease families, which are divided into 74 families in 17 groups. Researches on the sequence structure, family classification, biological activity and functional mechanism of metalloproteinases of these five types of poison-carrying animals were comprehensively described. It was found that metalloproteases of M10 family existed in the venom of parasitic wasps and jellyfishes, that of M13 family existed in the venom of parasitic wasps and scorpions, M12 family were commonly found in the venom of snakes, parasitic wasps, scorpions and jellyfishes. Researches of snake venom metalloproteinases were relatively deep and comprehensive, which had the activities and functions of degrading extracellular matrix proteins, regulating cells, inhibiting platelet aggregation and so on. The studies of venom metalloproteinases in scorpions, parasitic wasps, spiders and jellyfishes were relatively less, and their molecular structure, family classification, function and mechanism of action, were still unclear. The article can deepen scholars' understanding of venom metalloproteinases, and provide references for the future research direction of venom metalloproteinases, and lay the foundation for the application of venom metalloproteinases.

venom metalloproteinases; family classification; bioactivity; functional mechanism; research

10.3969/j.issn.2095-3704.2023.04.79

Q955

A

2095-3704（2023）04-0538-11

2023-10-03

2023-10-16

貴州省林業科研項目（黔林科合J字[2022]30號）和中央引導地方科技發展資金項目（黔科中引地[2019]4004號）

徐志文（1992—），男，工程師，碩士，主要從事農林資源保護與利用研究，978115111@qq.com；*通信作者：任雪敏，工程師，碩士，1685800140@qq.com。

徐志文, 任雪敏, 吳朝妍, 等. 5類有毒動物毒液金屬蛋白酶研究進展[J]. 生物災害科學, 2023, 46(4): 538-548.