// DOQCS : http://doqcs.ncbs.res.in/ // Accession Name = PLCbeta1 // Accession Number = 13 // Transcriber = Sridhar Hariharaputran, NCBS // Developer = Sridhar Hariharputran, NCBS // Species = Bovine; Mammalian // Tissue = Brain - Neuronal; expressed in E.coli // Cell Compartment = Cell Membrane // Notes = This is a model of PLCbeta1 in the bovine brain membranes as stimulated by Ca, Gq and PA.
The primary data sources are Irene Litosch Biochemistry (2000) 39(26):7736-43,
Sternweis PC et al. Philos Trans R Soc Lond B Biol Sci. (1992) 336(1276):35-41 and
Smrcka AV et al. Science (1991) 251(4995):804-7. //genesis // kkit Version 11 flat dumpfile // Saved on Thu Dec 8 14:11:19 2005 include kkit {argv 1} FASTDT = 0.0001 SIMDT = 0.001 CONTROLDT = 10 PLOTDT = 1 MAXTIME = 50 TRANSIENT_TIME = 2 VARIABLE_DT_FLAG = 1 DEFAULT_VOL = 1.6667e-21 VERSION = 11.0 setfield /file/modpath value /home2/bhalla/scripts/modulesaet kparms //genesis initdump -version 3 -ignoreorphans 1 simobjdump doqcsinfo filename accessname accesstype transcriber developer \ citation species tissue cellcompartment methodology sources \ model_implementation model_validation x y z simobjdump table input output alloced step_mode stepsize x y z simobjdump xtree path script namemode sizescale simobjdump xcoredraw xmin xmax ymin ymax simobjdump xtext editable simobjdump xgraph xmin xmax ymin ymax overlay simobjdump xplot pixflags script fg ysquish do_slope wy simobjdump group xtree_fg_req xtree_textfg_req plotfield expanded movealone \ link savename file version md5sum mod_save_flag x y z simobjdump geometry size dim shape outside xtree_fg_req xtree_textfg_req x y \ z simobjdump kpool DiffConst CoInit Co n nInit mwt nMin vol slave_enable \ geomname xtree_fg_req xtree_textfg_req x y z simobjdump kreac kf kb notes xtree_fg_req xtree_textfg_req x y z simobjdump kenz CoComplexInit CoComplex nComplexInit nComplex vol k1 k2 k3 \ keepconc usecomplex notes xtree_fg_req xtree_textfg_req link x y z simobjdump stim level1 width1 delay1 level2 width2 delay2 baselevel trig_time \ trig_mode notes xtree_fg_req xtree_textfg_req is_running x y z simobjdump xtab input output alloced step_mode stepsize notes editfunc \ xtree_fg_req xtree_textfg_req baselevel last_x last_y is_running x y z simobjdump kchan perm gmax Vm is_active use_nernst notes xtree_fg_req \ xtree_textfg_req x y z simobjdump transport input output alloced step_mode stepsize dt delay clock \ kf xtree_fg_req xtree_textfg_req x y z simobjdump proto x y z simundump geometry /kinetics/geometry 0 1.6667e-21 3 sphere "" white black \ -502 -473 0 simundump group /kinetics/PLCbeta 0 yellow black x 0 0 "" PLCbeta \ /home2/bhalla/scripts/modulesaet/PLCbeta_0.g 0 0 0 -532 -472 0 simundump kpool /kinetics/PLCbeta/PLCbeta 0 0 0.12 0.12 0.12 0.12 0 0 1 0 \ /kinetics/geometry 31 yellow -525 -470 0 simundump kreac /kinetics/PLCbeta/Gq-bind-Ca.PLCbeta 0 50 1 "" 1 yellow -526 \ -472 0 simundump kpool /kinetics/PLCbeta/Ca.PLCbeta 0 0 0 0 0 0 0 0 1 0 \ /kinetics/geometry 10 yellow -519 -474 0 simundump kenz /kinetics/PLCbeta/Ca.PLCbeta/Ca.PLCbeta 0 0 0 0 0 1 3.5 28 7 0 \ 1 "" red 10 "" -519 -475 0 simundump kreac /kinetics/PLCbeta/Ca_bind_PLCbeta 0 1 1 "" 17 yellow -519 \ -472 0 simundump kreac /kinetics/PLCbeta/PA-bind-Ca.PLCbeta 0 1 8 "" 60 yellow -512 \ -472 0 simundump kpool /kinetics/PLCbeta/PA.Ca.PLCbeta 0 0 0 0 0 0 0 0 1 0 \ /kinetics/geometry 47 yellow -508 -474 0 simundump kenz /kinetics/PLCbeta/PA.Ca.PLCbeta/PA.Ca.PLCbeta 0 0 0 0 0 1 19 \ 152 38 0 1 "" red 47 "" -508 -475 0 simundump kpool /kinetics/PLCbeta/PIP2 0 0 25 25 25 25 0 0 1 4 \ /kinetics/geometry 1 yellow -519 -478 0 simundump kreac /kinetics/PLCbeta/Basal 0 0.009 0 "" white yellow -519 -481 0 simundump kpool /kinetics/PLCbeta/Gq 0 0 0 0 0 0 0 0 1 0 /kinetics/geometry \ 45 yellow -530 -470 0 simundump kpool /kinetics/PLCbeta/Ca 0 0 0.09 0.09 0.09 0.09 0 0 1 4 \ /kinetics/geometry 59 yellow -513 -470 0 simundump kpool /kinetics/PLCbeta/PA 0 0 1 1 1 1 0 0 1 0 /kinetics/geometry 1 \ yellow -508 -470 0 simundump kpool /kinetics/PLCbeta/DAG 0 0 0 0 0 0 0 0 1 0 /kinetics/geometry \ 61 yellow -508 -478 0 simundump kpool /kinetics/PLCbeta/IP3 0 0 0 0 0 0 0 0 1 0 /kinetics/geometry \ blue yellow -530 -478 0 simundump kpool /kinetics/PLCbeta/Gq.Ca.PLCbeta 0 0 0 0 0 0 0 0 1 0 \ /kinetics/geometry 61 yellow -530 -474 0 simundump kenz /kinetics/PLCbeta/Gq.Ca.PLCbeta/Gq.Ca.PLCbeta 0 0 0 0 0 1 11.5 \ 92 23 0 0 "" red 61 "" -530 -475 0 simundump doqcsinfo /kinetics/doqcsinfo 0 db13.g PLCbeta1putran pathway \ "Sridhar Hariharaputran, NCBS" "Sridhar Hariharputran, NCBS" \ "citation here" "Bovine ; Mammalian" \ "Brain - Neuronal; expressed in E.coli" "Cell Membrane" Qualitative \ In-house "Exact GENESIS implementation" "Approximates original data " -501 \ -471 0 simundump xgraph /graphs/conc1 0 0 50 -0.25 4.75 0 simundump xgraph /graphs/conc2 0 0 50 0 5 0 simundump xplot /graphs/conc1/Ca.Co 3 524288 \ "delete_plot.w ; edit_plot.D " 59 0 0 1 simundump xplot /graphs/conc1/PLCbeta.Co 3 524288 \ "delete_plot.w ; edit_plot.D " 31 0 0 1 simundump xplot /graphs/conc1/IP3.Co 3 524288 \ "delete_plot.w ; edit_plot.D " blue 0 0 1 simundump xplot /graphs/conc2/PA.Co 3 524288 \ "delete_plot.w ; edit_plot.D " 1 0 0 1 simundump xplot /graphs/conc2/DAG.Co 3 524288 \ "delete_plot.w ; edit_plot.D " 61 0 0 1 simundump xgraph /moregraphs/conc3 0 0 50 0 1 0 simundump xgraph /moregraphs/conc4 0 0 50 0 0.1 0 simundump xcoredraw /edit/draw 0 -534 -496 -483 -468 simundump xtree /edit/draw/tree 0 \ /kinetics/#[],/kinetics/#[]/#[],/kinetics/#[]/#[]/#[][TYPE!=proto],/kinetics/#[]/#[]/#[][TYPE!=linkinfo]/##[] \ "edit_elm.D ; drag_from_edit.w " auto 0.6 simundump xtext /file/notes 0 1 xtextload /file/notes \ "8 Nov 2001" \ " " \ " This is the functional model" addmsg /kinetics/PLCbeta/Ca_bind_PLCbeta /kinetics/PLCbeta/PLCbeta REAC A B addmsg /kinetics/PLCbeta/Gq /kinetics/PLCbeta/Gq-bind-Ca.PLCbeta SUBSTRATE n addmsg /kinetics/PLCbeta/Ca.PLCbeta /kinetics/PLCbeta/Gq-bind-Ca.PLCbeta SUBSTRATE n addmsg /kinetics/PLCbeta/Gq.Ca.PLCbeta /kinetics/PLCbeta/Gq-bind-Ca.PLCbeta PRODUCT n addmsg /kinetics/PLCbeta/Ca_bind_PLCbeta /kinetics/PLCbeta/Ca.PLCbeta REAC B A addmsg /kinetics/PLCbeta/Gq-bind-Ca.PLCbeta /kinetics/PLCbeta/Ca.PLCbeta REAC A B addmsg /kinetics/PLCbeta/PA-bind-Ca.PLCbeta /kinetics/PLCbeta/Ca.PLCbeta REAC A B addmsg /kinetics/PLCbeta/Ca.PLCbeta /kinetics/PLCbeta/Ca.PLCbeta/Ca.PLCbeta ENZYME n addmsg /kinetics/PLCbeta/PIP2 /kinetics/PLCbeta/Ca.PLCbeta/Ca.PLCbeta SUBSTRATE n addmsg /kinetics/PLCbeta/Ca /kinetics/PLCbeta/Ca_bind_PLCbeta SUBSTRATE n addmsg /kinetics/PLCbeta/Ca.PLCbeta /kinetics/PLCbeta/Ca_bind_PLCbeta PRODUCT n addmsg /kinetics/PLCbeta/PLCbeta /kinetics/PLCbeta/Ca_bind_PLCbeta SUBSTRATE n addmsg /kinetics/PLCbeta/PA /kinetics/PLCbeta/PA-bind-Ca.PLCbeta SUBSTRATE n addmsg /kinetics/PLCbeta/Ca.PLCbeta /kinetics/PLCbeta/PA-bind-Ca.PLCbeta SUBSTRATE n addmsg /kinetics/PLCbeta/PA.Ca.PLCbeta /kinetics/PLCbeta/PA-bind-Ca.PLCbeta PRODUCT n addmsg /kinetics/PLCbeta/PA-bind-Ca.PLCbeta /kinetics/PLCbeta/PA.Ca.PLCbeta REAC B A addmsg /kinetics/PLCbeta/PA.Ca.PLCbeta /kinetics/PLCbeta/PA.Ca.PLCbeta/PA.Ca.PLCbeta ENZYME n addmsg /kinetics/PLCbeta/PIP2 /kinetics/PLCbeta/PA.Ca.PLCbeta/PA.Ca.PLCbeta SUBSTRATE n addmsg /kinetics/PLCbeta/Ca.PLCbeta/Ca.PLCbeta /kinetics/PLCbeta/PIP2 REAC sA B addmsg /kinetics/PLCbeta/Gq.Ca.PLCbeta/Gq.Ca.PLCbeta /kinetics/PLCbeta/PIP2 REAC sA B addmsg /kinetics/PLCbeta/PA.Ca.PLCbeta/PA.Ca.PLCbeta /kinetics/PLCbeta/PIP2 REAC sA B addmsg /kinetics/PLCbeta/Basal /kinetics/PLCbeta/PIP2 REAC A B addmsg /kinetics/PLCbeta/PIP2 /kinetics/PLCbeta/Basal SUBSTRATE n addmsg /kinetics/PLCbeta/DAG /kinetics/PLCbeta/Basal PRODUCT n addmsg /kinetics/PLCbeta/IP3 /kinetics/PLCbeta/Basal PRODUCT n addmsg /kinetics/PLCbeta/Gq-bind-Ca.PLCbeta /kinetics/PLCbeta/Gq REAC A B addmsg /kinetics/PLCbeta/Ca_bind_PLCbeta /kinetics/PLCbeta/Ca REAC A B addmsg /kinetics/PLCbeta/PA-bind-Ca.PLCbeta /kinetics/PLCbeta/PA REAC A B addmsg /kinetics/PLCbeta/Ca.PLCbeta/Ca.PLCbeta /kinetics/PLCbeta/DAG MM_PRD pA addmsg /kinetics/PLCbeta/Gq.Ca.PLCbeta/Gq.Ca.PLCbeta /kinetics/PLCbeta/DAG MM_PRD pA addmsg /kinetics/PLCbeta/PA.Ca.PLCbeta/PA.Ca.PLCbeta /kinetics/PLCbeta/DAG MM_PRD pA addmsg /kinetics/PLCbeta/Basal /kinetics/PLCbeta/DAG REAC B A addmsg /kinetics/PLCbeta/Ca.PLCbeta/Ca.PLCbeta /kinetics/PLCbeta/IP3 MM_PRD pA addmsg /kinetics/PLCbeta/Gq.Ca.PLCbeta/Gq.Ca.PLCbeta /kinetics/PLCbeta/IP3 MM_PRD pA addmsg /kinetics/PLCbeta/PA.Ca.PLCbeta/PA.Ca.PLCbeta /kinetics/PLCbeta/IP3 MM_PRD pA addmsg /kinetics/PLCbeta/Basal /kinetics/PLCbeta/IP3 REAC B A addmsg /kinetics/PLCbeta/Gq-bind-Ca.PLCbeta /kinetics/PLCbeta/Gq.Ca.PLCbeta REAC B A addmsg /kinetics/PLCbeta/Gq.Ca.PLCbeta/Gq.Ca.PLCbeta /kinetics/PLCbeta/Gq.Ca.PLCbeta REAC eA B addmsg /kinetics/PLCbeta/Gq.Ca.PLCbeta /kinetics/PLCbeta/Gq.Ca.PLCbeta/Gq.Ca.PLCbeta ENZYME n addmsg /kinetics/PLCbeta/PIP2 /kinetics/PLCbeta/Gq.Ca.PLCbeta/Gq.Ca.PLCbeta SUBSTRATE n addmsg /kinetics/PLCbeta/Ca /graphs/conc1/Ca.Co PLOT Co *Ca.Co *59 addmsg /kinetics/PLCbeta/PLCbeta /graphs/conc1/PLCbeta.Co PLOT Co *PLCbeta.Co *31 addmsg /kinetics/PLCbeta/IP3 /graphs/conc1/IP3.Co PLOT Co *IP3.Co *blue addmsg /kinetics/PLCbeta/PA /graphs/conc2/PA.Co PLOT Co *PA.Co *1 addmsg /kinetics/PLCbeta/DAG /graphs/conc2/DAG.Co PLOT Co *DAG.Co *61 enddump // End of dump call /kinetics/PLCbeta/notes LOAD \ "4 Oct 2001" \ "----------" \ " Initial version incorporating inputs of" \ "Ca, Gq and PA. The PA is still problematic at very high" \ "or very low levels of Ca but works OK in the range 0.1 to" \ "1 uM. PA data primarily from " \ "Litosch 2000 Biochemistry 39:7736-7743." \ "Gq data primarily from Sternweis et al 1992 Phil Trans" \ "Roy Soc Lond B Biol Sci 29;336(1276): 35-41 and" \ "Smrcka et al Science 251 804-807 1991." \ "Model parameter specification H. Sridhar 2001." \ "" call /kinetics/PLCbeta/PLCbeta/notes LOAD \ "12 Jul 2001" \ "" \ "The Concentration PLC-beta is set to 0.12 " \ "obtained from " \ "Ryu etal 1987, Jour.Bio.Chem, 12511-12518, 1987." call /kinetics/PLCbeta/Gq-bind-Ca.PLCbeta/notes LOAD \ "6 Nov 2001" \ "" \ "The Kf and Kb values were fixed according to the response" \ "curves obtained from " \ "I. Litosch, Biochem., 2000, 39, 7736-7743." call /kinetics/PLCbeta/Ca.PLCbeta/notes LOAD \ "6 Nov 2001" \ "" \ "The enzyme activity is observed only when it combines with Ca " \ "and becomes Calcium bound form of enzyme complex.All the" \ "curves obtained are in the presence of different concentrations" \ "of Calcium by" \ "I. Litosch, Biochem.,2000, 39,7736-7743. " call /kinetics/PLCbeta/Ca.PLCbeta/Ca.PLCbeta/notes LOAD \ "3 Nov 2001" \ "" \ "Sternweis et al Phil Trans Soc R Lond B Biol Sci 1992 Apr 29;" \ "336(1276);35-41;discussion 41-2." \ "The Km and Vmax values according to Sternweis et al." \ "The Km is fixed to 10uM since there is absence of Gq and so" \ "is the Vmax values which is fixed at 7uM since the Km obtained" \ "varies between 5 and 20uM and Vmax between 7 and 23umol/min/mg" \ "depending on the presence and absence of Gq." call /kinetics/PLCbeta/Ca_bind_PLCbeta/notes LOAD \ "6 Nov 2001" \ "" \ "The Kf and Kb values were fixed according to the dose response" \ "curves obtained from " \ "I.Litosch, Biochem., 2000, 39, 7736-7743." call /kinetics/PLCbeta/PA-bind-Ca.PLCbeta/notes LOAD \ "6 Nov 2001" \ "" \ "The Kf and Kb values were fixed according to the dose response" \ "curves obtained from" \ "I. Litosch, Biochem., 2000, 39, 7736-7743." call /kinetics/PLCbeta/PA.Ca.PLCbeta/notes LOAD \ "6 Nov 2001" \ "" \ "This is the active enzyme complex formed by binding of" \ "PA with Ca.PLCbeta.All the activity of PA is possible only" \ "in the presence of Calcium bound enzyme i.e., Ca.PLCbeta " \ "and resulted in dose response curves for the activity" \ "obtained by" \ " I. Litosch., Biochem., 2000, 39, 7736-7743." call /kinetics/PLCbeta/PA.Ca.PLCbeta/PA.Ca.PLCbeta/notes LOAD \ "3 Nov 2001" \ "" \ "The Km and Vmax were fixed relatively to the Km and Vmax " \ "values of Ca.PLCbeta and Gq.Ca.PLCbeta which were obtained" \ "from the works of Sternweis et al and Smrcka et al where" \ "the Km varied between 5 and 20uM and Vmax between 7 and 23" \ "umol/min/mg depending on the presence and absence of Gq." call /kinetics/PLCbeta/PIP2/notes LOAD \ "12 Jul 2001" \ " " \ "The PIP2 concentration is fixed to 25uM and is buffered to" \ "maitain the same level of substrate." \ "I. Liotsch, Biochem., 2000, 39, 7736-7743." call /kinetics/PLCbeta/Basal/notes LOAD \ "6 Nov 2001" \ "" \ "The basal reaction rates are fixed according to the respomse" \ "curves obtained from" \ "I. Litosch, Biochem.,2000, 39, 7736-7743." call /kinetics/PLCbeta/Gq/notes LOAD \ "6 Nov 2001" \ "" \ "The Gq concentration is fixed to 0 since the response " \ "curves obtained by I. Litosch, Biochem. 2000, 39, 7736-7743" \ "are in the absence of Gq.The concentration of Gq is fixed to" \ "1uM when it is present." call /kinetics/PLCbeta/Ca/notes LOAD \ "21 Jul 2001" \ "" \ "Concn varies betwn 0.001 to 10 uM." \ "The Concentration of Ca is obtained from " \ "I. Litosch, Biochem., 2000, 39,7736-7743." \ "" \ "The concentration of Ca is buffered to different levels" \ "and rate of binding of enzyme is noted.But here it is set to" \ "0.09uM which is the basal level of Calcium." call /kinetics/PLCbeta/PA/notes LOAD \ "12 Jul 2001" \ "" \ "The Concentration of Phosphatidic Acid is obtained from " \ "I. Liotsch, Biochem., 2000, 39, 7736-7743." \ "" \ "The PA concentration vary between 0-60uM" \ "Usually the concn levels are set to the basal levels" \ "which are under 2 mole percent, estimated at 1 uM." call /kinetics/PLCbeta/DAG/notes LOAD \ "6 Nov 2001" \ "" \ "DAG: diacylglycerol." call /kinetics/PLCbeta/IP3/notes LOAD \ "6 Nov 2001" \ "IP3: Inositol Trisphosphate." \ "" \ "Here we do not model the metabolism of IP3." call /kinetics/PLCbeta/Gq.Ca.PLCbeta/notes LOAD \ "6 Nov 2001" \ "" \ "This active enzyme is complex formed by binding of Gq with " \ "Ca.PLCbeta where concentration formed is 0 because of the" \ "absence of Gq.The response curves are obtained in the absence " \ "of Gq by I.Litosch, Biochem. 2000, 39,7736-7743. " \ "" call /kinetics/PLCbeta/Gq.Ca.PLCbeta/Gq.Ca.PLCbeta/notes LOAD \ "3 Nov 2001" \ "" \ "The Km and Vmax values are fixed accordingly from " \ "Sternweis et al Phil Trans R Soc Lond B Bio Sci 1992" \ "Apr 29;336(1276):35-41;discussion 41-2 and" \ "Smrcka et al Science 251 804-807 1991" \ "where Km varied between 5 and 20uM and Vmax between 7 and 23" \ "umol/min/mg depending on the presenece and absence of Gq." call /kinetics/doqcsinfo/notes LOAD \ "This is a model of PLCbeta1 in the bovine brain membranes as stimulated by Ca, Gq and PA.
The primary data sources are Irene Litosch Biochemistry (2000) 39(26):7736-43,
Sternweis PC et al. Philos Trans R Soc Lond B Biol Sci. (1992) 336(1276):35-41 and
Smrcka AV et al. Science (1991) 251(4995):804-7." complete_loading