ELSA REINER

MAJA KATALINIĆ

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About 30 years of organising international meetingscholinesterases and related enzymesThis paper summarizes a series of international meetings on choli-nesterases and related enzymes initiated by the Institute for Medi-cal Research and Occupational Health (IMI) over the past decades.Since their discovery in the 1930s, the enzymes belonging to thecholinesterase family (ChEs), acetylcholinesterase (AChE, EC 3.1.1.7)and butyrylcholinesterase (BChE, EC 3.1.1.8), have been in focus ofmany studies in biochemistry, physiology, biomedicine and toxicology.AChE and BChE own their enzyme activity to the catalytic triadserine-hystidine-glutamic acid, positioned at the bottom of the activesite enzyme gorge (Figure 1). The physiological role of AChE is to hy-drolyse acetylcholine (ACh) released into the synapse as a neurotrans-mitter. The hydrolysis of released ACh must occur before the next re-leased ACh reaches the cholinergic receptor, because accumulation ofACh in the synapse is toxic. The physiological role of BChE is not yetfully clarified. However, BChE can hydrolyse ACh and many xeno-biotics. Organophosphorus (OP) compounds are potent inhibitors ofChEs because they bind covalently to the serine of the catalytic triad.Inhibition of ChEs by OPs is therefore toxic. OP compounds are usedas pesticides, some compounds also as drugs, but some are being mis-used as warfare nerve agents (Figure 2). Enzymes related to choli-nesterses, named paraoxonase and DFP-ase, hydrolyse OP compoundsand thereby act as antidotes against OP poisoning.Way back in 1975, we organised the first meeting on cholinesterasesthat also included cholinergic mechanisms. The meeting was held inSplit. Participation was by invitation only, and 45 participants from 13countries convened. The meeting created considerable interest and re-sulted as the beginning of two series of international meetings beingheld up to the present date. Since Split, participation was not limited toinvitations only. ChE meetings take place in different countries and ondifferent continents thereby creating »a family« of participants that iscontinually growing and hopefully helping fruitful collaboration andadvances in the field.The list of cholinesterase meetings is given in Table 1a and the list ofpublished proceedings is given in Table 1b. The 11th ChE meeting isplanned to be held in Kazan, Russia, in June 2012. Meetings oncholinergic mechanisms developed as a separate series. The 13th meet-ing was in Foz du Iquacu, Parana, Brazil in August 2008, and the nextis planned to take place in Kyoto, Japan, in September 2012.The threat of misusing OP compounds stimulated us to start in par-allel a separate series of meetings on enzymes hydrolysing these com-pounds. The list of the first three meetings on esterases reacting withELSA REINERMAJA KATALINI]Institute for Medical Researchand Occupational HealthPOB 291, HR-10001 Zagreb, CroatiaCorrespondence:Elsa Reiner, Ph. D.Institute for Medical Researchand Occupational HealthKsaverska c. 2, POB 291HR-10000 Zagreb, CroatiaE-mail: ereiner@imi.hrReceived February 28, 2011.PERIODICUM BIOLOGORUM UDC 57:61VOL. 113, No 1, 17–20, 2011 CODEN PDBIADISSN 0031-5362Science policyorganophosphorus compounds is given in Table 2a andthe list of published proceedings is given in Table 2b. Allthree meetings were planned to take place in the Inter-university Center in Dubrovnik, however, due to the waragainst Croatia, the second meeting was held in Italythanks to the kind help obtained from Marcello Lotti(Padova, Italy).One topic discussed during these meetings was theclassification of enzymes hydrolysing OPs and therebydetoxifying these compounds. The Nomenclature Com-mittee of the International Union of Biochemistry andMolecular Biology accepted our recommendation con-cerning the classification (W. N. Aldridge, F. C. G. Ho-skin, E. Reiner, C. H. Walker (1989) Suggestions for anomenclature and classification of enzymes hydrolysingorganophosphorus compounds. In: E. Reiner, W. N. Ald-ridge, F. C. G. Hoskin (Eds.) Enzymes HydrolysingOrganophosphorus Compounds. Ellis Horwood Limi-ted, Chichester, England, pp 246–253), and since 1992these enzymes are classified as phosphoric triester hydro-lases EC 3.1.8 with two subgroups: paraoxonase EC3.1.8.1 and DFP-ase EC 3.1.8.2 (Enzyme Nomencla-ture, Recommendations of the Nomenclature Commit-tee of the International Union of Biochemistry and Mo-lecular Biology (prepared by E. C. Webb). AcademicPress, Inc., San Diego, USA, 1992, p. 336). This series ofmeetings is also continuing to the present date, but fo-cusing mostly on paraoxonases. The numbering of meet-ings that continued, however, started again from No. 1.The 4th meeting was held in La Pineda, Catalonia, Spain,in September 2010, and the next meeting has been an-nounced, but place and date not yet decided.The 10th ChE was for us a jubilee meeting not onlybecause it was the 10th but because the meeting venuewas again in Croatia. The meeting coorganiser was theCroatian Society of Biochemistry and Molecular Biol-ogy, and the meeting was held under the auspices of theCroatian Academy of Science and Arts. The meeting wasattended by 204 participants from 28 countries. The prog-ramme covered a broad range of topics beginning withbasic structure of cholinesterases, molecular and cell bi-ology, mechanisms of interactions, up to the newly de-bated alternative (noncholinergic) functions of cholin-esterases. The meeting also covered topics on enzymeshydrolysing OP compounds as well as diseases, Alzhei-mer and Parkinson disease, linked to the ChE activity.For the first time the programme included a 3D-sessionfor the presentation of structural aspects of enzymes instereoscopic 3D technique. The proceeding (Table 1b,ref. (10)) comprises 80 manuscripts from oral and posterpresentations given at the 10th ChE meeting. The ple-nary lecturer Palmer Taylor (San Diego, USA) summa-rised the major achievements since the Split meeting in alecture entitled »From Split to [ibenik: The tortuouspathway in the cholinesterase field« giving thereby a his-torical background to the ChE meetings (Table 1b, ref.(10) pages 3–9).We hope that the series of meetings will continue sup-porting worldwide advancements in research, fruitfulcollaboration and lasting friendships.18 Period biol, Vol 113, No 1, 2011.Elsa Reiner and Maja Katalini} Cholinesterases and related enzymesFigure 1. Schematic presentation of AChE and BChE structures with indicated b-sheets (blue-green) and a-helixes (red). Amino acids of the activesite catalytic triad (Ser-His-Glu) are indicated in dark gray (AChE PDB code 3LII, BChE PDB code 2PM8). (Prepared by Goran [inko, IMI,Zagreb).POOFPOOFPOSONPOONCNSARIN SOMAN TABUN VXFigure 2. Structure of four organophosphorus warfare nerve agents.Period biol, Vol 113, No 1, 2011. 19Cholinesterases and related enzymes Elsa Reiner and Maja Katalini}TABLE 1aList of international meetings on cholinesterases.Meeting Year Place Main Organizers Proceedings reference1st 1975 Split, Croatia Elsa Reiner (Croatia) (1)2nd 1983 Bled, Slovenia Miro Brzin (Slovenia) (2)3rd 1990 La Grande Motte, France Jean-Pierre Toutant (France) (3)4th 1992 Eilat, Israel Avigdor Shafferman (Israel)Baruch Velan (Israel)(4)5th 1994 Madras, India A. Balasubramanian (India)Bhupendra P. Doctor (USA)(5)6th 1998 La Jolla, USA Palmer Taylor (USA) (6)7th 2002 Pucon, Chile Nibaldo Inestrosa (Chile) (7)8th 2004 Perugia, Italy Vincenzo N. Talesa (Italy) (8)9th 2007 Suzhou, China Karl W.K. Tsim (China) (9)10th 2009 [ibenik, Croatia Elsa Reiner (Croatia)Zrinka Kovarik (Croatia)(10)TABLE 1bList of proceedings references.No. Proceedings references(1) Cholinesterases and Cholinergic ReceptorsEds.: E. Reiner; Subeds.: M. [krinjari}-[poljar, V. SimeonCroatica Chemica Acta 47 (1975) 163–506Croatian Chemical Society, Zagreb, Croatia(2) Cholinesterases, Fundamental and Applied AspectsEds.: M. Brzin, E. A. Barnard, D. SketWalter De Gruyter, Berlin, New York, USA (1984) pp 1–526(3) Cholinesterases: Structure, Function, Mechanism, Genetics, and Cell Biology (ACS Conference Proceedings Series)Eds.: J. Massoulié, E. Barnard, A. Chatonnet, F. Bacou, B. P. Doctor, D. M. QuinnAmerican Chemical Society, Washington, USA (1991) pp 1–414(4) Multidisciplinary Approaches to Cholinesterase FunctionsEds.: A. Shafferman, B. VelanPlenum Press, New York, USA (1992) pp 1–293(5) Enzymes of the Cholinesterase FamilyEds.: A.S. Balasubramanian, B. P. Doctor, D. M. Quinn, P. TaylorPlenum Press, New York, USA (1995) pp 1–534(6) Structure and Function of Cholinesterases and Related ProteinsEds.: B. P. Doctor, P. Taylor, D. M. Quinn, R. L. Rotundo, M. K. GentryPlenum Press, New York, USA (1998) pp 1–630(7) Cholinesterases in the Second Millennium: Biomolecular and Pathological AspectEds.: N. Inestrosa, E. O. CamposP. Universidada Catolica de Chile – FONDAP Biomedicina, Chile (2004) pp 1–384(8) Proceedings of the VIII International Meeting on CholinesterasesGuest Eds.: V. N. Talesa, C. AntognelliChemico-Biological Interactions – Special Issue 157–158 (2005) 1–434Elsevier Ireland Ltd.(9) Proceedings of the IX International Meeting on CholinesterasesGuest Eds.: K. W. K. Tsim, B. P. Doctor, N. L. SiowChemico-Biological Interactions – Special Issue 175/1–3 (2008) 1–430Elsevier Ireland Ltd.(10) Proceeding of the 10th International Meeting on CholinesterasesGuest Eds.: E. Reiner, J. Massoulié, T. Rosenberry, P. Eyer, G. Amitai, Z. Radi}, Z. Kovarik; Assistant to Guest Eds.: M. Katalini}Chemico-Biological Interactions – Special Issue 187/1–3 (2010) 1–446Elsevier Ireland Ltd.20 Period biol, Vol 113, No 1, 2011.Elsa Reiner and Maja Katalini} Cholinesterases and related enzymesTABLE 2aList of international meetings on esterases reacting with organophosphorus compounds.Meeting Year Place Main Organizers Proceedings reference1st 1988 Dubrovnik, Croatia Elsa Reiner (Croatia)W. Norman Aldridge (UK)Francis C. G. Hoskin (USA)(1)2nd 1992 Salsomaggiore, Italy Elsa Reiner (Croatia)Marcello Lotti (Italy)(2)3rd 1998 Dubrovnik, Croatia Elsa Reiner (Croatia) (3)TABLE 2bList of proceedings references.No. Proceedings references(1) Enzymes Hydrolysing Organophosphorus Compounds Eds.: E. Reiner, W. N. Aldridge, F. C. G. HoskinEllis Horwood Limited, Chichester, England (1989) pp 1–266(2) Enzymes Intereacting with Organophosphorus CompoundsGuest Eds.: E. Reiner, M. Lotti; Associate Guest Eds.: M. K. Johnson, V. Simeon, A. Moretto; Consulting Ed.: E. HodgsonChemico-Biological Interactions – Special Issue 87 (1993) 1–476Elsevier Scientific Publisher Ireland Ltd.(3) Esterases Reacting with Organophosphorus CompoundsGuest Eds.: E. Reiner, V. Simeon-Rudolf, B. P. Doctor, C. E. Furlong, M. K. Johnson, M. Lotti, I. Silman, P. TaylorChemico-Biological Interactions – Special Issue 119–120 (1999) 1–620Elsevier Science Ireland Ltd.

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About 30 years of organising international meetings cholinesterases and related enzymes

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About 30 years of organising international meetingscholinesterases and related enzymesThis paper summarizes a series of international meetings on choli-nesterases and related enzymes initiated by the Institute for Medi-cal Research and Occupational Health (IMI) over the past decades.Since their discovery in the 1930s, the enzymes belonging to thecholinesterase family (ChEs), acetylcholinesterase (AChE, EC 3.1.1.7)and butyrylcholinesterase (BChE, EC 3.1.1.8), have been in focus ofmany studies in biochemistry, physiology, biomedicine and toxicology.AChE and BChE own their enzyme activity to the catalytic triadserine-hystidine-glutamic acid, positioned at the bottom of the activesite enzyme gorge (Figure 1). The physiological role of AChE is to hy-drolyse acetylcholine (ACh) released into the synapse as a neurotrans-mitter. The hydrolysis of released ACh must occur before the next re-leased ACh reaches the cholinergic receptor, because accumulation ofACh in the synapse is toxic. The physiological role of BChE is not yetfully clarified. However, BChE can hydrolyse ACh and many xeno-biotics. Organophosphorus (OP) compounds are potent inhibitors ofChEs because they bind covalently to the serine of the catalytic triad.Inhibition of ChEs by OPs is therefore toxic. OP compounds are usedas pesticides, some compounds also as drugs, but some are being mis-used as warfare nerve agents (Figure 2). Enzymes related to choli-nesterses, named paraoxonase and DFP-ase, hydrolyse OP compoundsand thereby act as antidotes against OP poisoning.Way back in 1975, we organised the first meeting on cholinesterasesthat also included cholinergic mechanisms. The meeting was held inSplit. Participation was by invitation only, and 45 participants from 13countries convened. The meeting created considerable interest and re-sulted as the beginning of two series of international meetings beingheld up to the present date. Since Split, participation was not limited toinvitations only. ChE meetings take place in different countries and ondifferent continents thereby creating »a family« of participants that iscontinually growing and hopefully helping fruitful collaboration andadvances in the field.The list of cholinesterase meetings is given in Table 1a and the list ofpublished proceedings is given in Table 1b. The 11th ChE meeting isplanned to be held in Kazan, Russia, in June 2012. Meetings oncholinergic mechanisms developed as a separate series. The 13th meet-ing was in Foz du Iquacu, Parana, Brazil in August 2008, and the nextis planned to take place in Kyoto, Japan, in September 2012.The threat of misusing OP compounds stimulated us to start in par-allel a separate series of meetings on enzymes hydrolysing these com-pounds. The list of the first three meetings on esterases reacting withELSA REINERMAJA KATALINI]Institute for Medical Researchand Occupational HealthPOB 291, HR-10001 Zagreb, CroatiaCorrespondence:Elsa Reiner, Ph. D.Institute for Medical Researchand Occupational HealthKsaverska c. 2, POB 291HR-10000 Zagreb, CroatiaE-mail: ereiner@imi.hrReceived February 28, 2011.PERIODICUM BIOLOGORUM UDC 57:61VOL. 113, No 1, 17–20, 2011 CODEN PDBIADISSN 0031-5362Science policyorganophosphorus compounds is given in Table 2a andthe list of published proceedings is given in Table 2b. Allthree meetings were planned to take place in the Inter-university Center in Dubrovnik, however, due to the waragainst Croatia, the second meeting was held in Italythanks to the kind help obtained from Marcello Lotti(Padova, Italy).One topic discussed during these meetings was theclassification of enzymes hydrolysing OPs and therebydetoxifying these compounds. The Nomenclature Com-mittee of the International Union of Biochemistry andMolecular Biology accepted our recommendation con-cerning the classification (W. N. Aldridge, F. C. G. Ho-skin, E. Reiner, C. H. Walker (1989) Suggestions for anomenclature and classification of enzymes hydrolysingorganophosphorus compounds. In: E. Reiner, W. N. Ald-ridge, F. C. G. Hoskin (Eds.) Enzymes HydrolysingOrganophosphorus Compounds. Ellis Horwood Limi-ted, Chichester, England, pp 246–253), and since 1992these enzymes are classified as phosphoric triester hydro-lases EC 3.1.8 with two subgroups: paraoxonase EC3.1.8.1 and DFP-ase EC 3.1.8.2 (Enzyme Nomencla-ture, Recommendations of the Nomenclature Commit-tee of the International Union of Biochemistry and Mo-lecular Biology (prepared by E. C. Webb). AcademicPress, Inc., San Diego, USA, 1992, p. 336). This series ofmeetings is also continuing to the present date, but fo-cusing mostly on paraoxonases. The numbering of meet-ings that continued, however, started again from No. 1.The 4th meeting was held in La Pineda, Catalonia, Spain,in September 2010, and the next meeting has been an-nounced, but place and date not yet decided.The 10th ChE was for us a jubilee meeting not onlybecause it was the 10th but because the meeting venuewas again in Croatia. The meeting coorganiser was theCroatian Society of Biochemistry and Molecular Biol-ogy, and the meeting was held under the auspices of theCroatian Academy of Science and Arts. The meeting wasattended by 204 participants from 28 countries. The prog-ramme covered a broad range of topics beginning withbasic structure of cholinesterases, molecular and cell bi-ology, mechanisms of interactions, up to the newly de-bated alternative (noncholinergic) functions of cholin-esterases. The meeting also covered topics on enzymeshydrolysing OP compounds as well as diseases, Alzhei-mer and Parkinson disease, linked to the ChE activity.For the first time the programme included a 3D-sessionfor the presentation of structural aspects of enzymes instereoscopic 3D technique. The proceeding (Table 1b,ref. (10)) comprises 80 manuscripts from oral and posterpresentations given at the 10th ChE meeting. The ple-nary lecturer Palmer Taylor (San Diego, USA) summa-rised the major achievements since the Split meeting in alecture entitled »From Split to [ibenik: The tortuouspathway in the cholinesterase field« giving thereby a his-torical background to the ChE meetings (Table 1b, ref.(10) pages 3–9).We hope that the series of meetings will continue sup-porting worldwide advancements in research, fruitfulcollaboration and lasting friendships.18 Period biol, Vol 113, No 1, 2011.Elsa Reiner and Maja Katalini} Cholinesterases and related enzymesFigure 1. Schematic presentation of AChE and BChE structures with indicated b-sheets (blue-green) anda-helixes (red). Amino acids of the activesite catalytic triad (Ser-His-Glu) are indicated in dark gray (AChE PDB code 3LII, BChE PDB code 2PM8). (Prepared by Goran [inko, IMI,Zagreb).POOFPOOFPOSONPOONCNSARIN SOMAN TABUN VXFigure 2. Structure of four organophosphorus warfare nerve agents.Period biol, Vol 113, No 1, 2011. 19Cholinesterases and related enzymes Elsa Reiner and Maja Katalini}TABLE 1aList of international meetings on cholinesterases.Meeting Year Place Main Organizers Proceedings reference1st 1975 Split, Croatia Elsa Reiner (Croatia) (1)2nd 1983 Bled, Slovenia Miro Brzin (Slovenia) (2)3rd 1990 La Grande Motte, France Jean-Pierre Toutant (France) (3)4th 1992 Eilat, Israel Avigdor Shafferman (Israel)Baruch Velan (Israel)(4)5th 1994 Madras, India A. Balasubramanian (India)Bhupendra P. Doctor (USA)(5)6th 1998 La Jolla, USA Palmer Taylor (USA) (6)7th 2002 Pucon, Chile Nibaldo Inestrosa (Chile) (7)8th 2004 Perugia, Italy Vincenzo N. Talesa (Italy) (8)9th 2007 Suzhou, China Karl W.K. Tsim (China) (9)10th 2009 [ibenik, Croatia Elsa Reiner (Croatia)Zrinka Kovarik (Croatia)(10)TABLE 1bList of proceedings references.No. Proceedings references(1) Cholinesterases and Cholinergic ReceptorsEds.: E. Reiner; Subeds.: M. [krinjari}-[poljar, V. SimeonCroatica Chemica Acta 47 (1975) 163–506Croatian Chemical Society, Zagreb, Croatia(2) Cholinesterases, Fundamental and Applied AspectsEds.: M. Brzin, E. A. Barnard, D. SketWalter De Gruyter, Berlin, New York, USA (1984) pp 1–526(3) Cholinesterases: Structure, Function, Mechanism, Genetics, and Cell Biology (ACS Conference Proceedings Series)Eds.: J. Massoulié, E. Barnard, A. Chatonnet, F. Bacou, B. P. Doctor, D. M. QuinnAmerican Chemical Society, Washington, USA (1991) pp 1–414(4) Multidisciplinary Approaches to Cholinesterase FunctionsEds.: A. Shafferman, B. VelanPlenum Press, New York, USA (1992) pp 1–293(5) Enzymes of the Cholinesterase FamilyEds.: A.S. Balasubramanian, B. P. Doctor, D. M. Quinn, P. TaylorPlenum Press, New York, USA (1995) pp 1–534(6) Structure and Function of Cholinesterases and Related ProteinsEds.: B. P. Doctor, P. Taylor, D. M. Quinn, R. L. Rotundo, M. K. GentryPlenum Press, New York, USA (1998) pp 1–630(7) Cholinesterases in the Second Millennium: Biomolecular and Pathological AspectEds.: N. Inestrosa, E. O. CamposP. Universidada Catolica de Chile – FONDAP Biomedicina, Chile (2004) pp 1–384(8) Proceedings of the VIII International Meeting on CholinesterasesGuest Eds.: V. N. Talesa, C. AntognelliChemico-Biological Interactions – Special Issue 157–158 (2005) 1–434Elsevier Ireland Ltd.(9) Proceedings of the IX International Meeting on CholinesterasesGuest Eds.: K. W. K. Tsim, B. P. Doctor, N. L. SiowChemico-Biological Interactions – Special Issue 175/1–3 (2008) 1–430Elsevier Ireland Ltd.(10) Proceeding of the 10th International Meeting on CholinesterasesGuest Eds.: E. Reiner, J. Massoulié, T. Rosenberry, P. Eyer, G. Amitai, Z. Radi}, Z. Kovarik; Assistant to Guest Eds.: M. Katalini}Chemico-Biological Interactions – Special Issue 187/1–3 (2010) 1–446Elsevier Ireland Ltd.20 Period biol, Vol 113, No 1, 2011.Elsa Reiner and Maja Katalini} Cholinesterases and related enzymesTABLE 2aList of international meetings on esterases reacting with organophosphorus compounds.Meeting Year Place Main Organizers Proceedings reference1st 1988 Dubrovnik, Croatia Elsa Reiner (Croatia)W. Norman Aldridge (UK)Francis C. G. Hoskin (USA)(1)2nd 1992 Salsomaggiore, Italy Elsa Reiner (Croatia)Marcello Lotti (Italy)(2)3rd 1998 Dubrovnik, Croatia Elsa Reiner (Croatia) (3)TABLE 2bList of proceedings references.No. Proceedings references(1) Enzymes Hydrolysing Organophosphorus Compounds Eds.: E. Reiner, W. N. Aldridge, F. C. G. HoskinEllis Horwood Limited, Chichester, England (1989) pp 1–266(2) Enzymes Intereacting with Organophosphorus CompoundsGuest Eds.: E. Reiner, M. Lotti; Associate Guest Eds.: M. K. Johnson, V. Simeon, A. Moretto; Consulting Ed.: E. HodgsonChemico-Biological Interactions – Special Issue 87 (1993) 1–476Elsevier Scientific Publisher Ireland Ltd.(3) Esterases Reacting with Organophosphorus CompoundsGuest Eds.: E. Reiner, V. Simeon-Rudolf, B. P. Doctor, C. E. Furlong, M. K. Johnson, M. Lotti, I. Silman, P. TaylorChemico-Biological Interactions – Special Issue 119–120 (1999) 1–620Elsevier Science Ireland Ltd.

About 30 years of organising international meetings cholinesterases and related enzymes

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