// 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