TABLE 1

Summary of effects on GLP-1 pharmacology (affinity and ability to activate cAMP pathway) in published site-directed mutagenesis studies of GLP-1R

WT (wild-type) refers to mutations that resulted in either <fivefold or no statistically significant change from wild-type GLP-1R. ND (not determinable) refers to a property that was measured, but for which a value was not determinable. Blank cells mean that the assays used to estimate that particular pharmacological property were not carried out in the cited work. Residues with symbol † refer to data from rat GLP-1R (if different, the equivalent human residue number is displayed in the table to aid comparison). GLP-1 affinity or potency fold-change values with suffix M are from membrane preparations, whereas suffix C is from whole-cell assays. Cell surface expression values below 75% of WT are shown (>75% are shown as WT): a suffix E represents estimation from ELISAs; suffix mic was evaluated from immunofluorescent microscopy; suffix cyt was evaluated by flow cytometry with an anti-Flag antibody; suffix Ag refers to affinity or cell surface expression levels determined from agonist radioligand-binding assays, whereas suffix Ant was from antagonist radioligand-binding assays. ΔLog τc values relative to WT are shown where >0.5 and were calculated from data where the expression-corrected efficacy term τc had been calculated using the operational model of agonism, as defined in Wootten et al. (2013c). Residues with transmembrane helices are numbered according to Wootten et al. (2013c).

ResidueMutated to-Fold Reduction Affinity-Fold Reduction Potency‡Cell Surface Expression (% Wild-Type)Comments and/or Other Observed EffectsReference
P7ECDLWTC,AntWTWTEKoole et al., 2011
R20ECDKWTC,AntWTWTEKoole et al., 2011
L32ECDAWTM,AgWTWTAgUnderwood et al., 2010
L32ECDAWTPatterson et al., 2013
W33ECDSWTC,AntSpecies change (human to rat)— the expected lack of effect on GLP-1 pharmacology was implied in text, but no data are shownTibaduiza et al., 2001
T35ECDAWT7%AgUnderwood et al., 2010
Val-36ECDAWTM,AgWTWTAgUnderwood et al., 2010
W39ECD†NDC,AgMembrane expression confirmed via WBWilmen et al., 1997
R44ECDHWTC,AntWTWTEKoole et al., 2011
N63ECDLWTC,AgWTWTAgChen et al., 2010a
E68ECDAWTM,AgWTWTAgUnderwood et al., 2010
E68ECDK8Day et al., 2011
Y69ECDANDM,AgNDNDAgUnderwood et al., 2010
W72ECD†NDC,AgMembrane expression confirmed via WBWilmen et al., 1997
N82ECDLWTC,AgWTWTAgChen et al., 2010a
W87ECDWTC,AgWT24–62%Transient and stable cell lines analyzedWilmen et al., 1997
Y88ECDANDM,AgNDNDAgUnderwood et al., 2010
L89ECDANDM,AgNDNDAgUnderwood et al., 2010
Pro-90ECDAWTM,AgWTWTAgUnderwood et al., 2010
W91ECD†NDC,AgMembrane expression confirmed via WBWilmen et al., 1997
W110ECD†NDC,AgMembrane expression confirmed via WBWilmen et al., 1997
N115ECDLWTC,AgWTWTAgChen et al., 2010a
W120ECD†NDC,AgMembrane expression confirmed via WBWilmen et al., 1997
R121ECDAWTM,AgWTWTAgUnderwood et al., 2010
L123ECDAWTM,AgWT47%AgUnderwood et al., 2010
E127ECDAWTM,AgWTWTAgUnderwood et al., 2010
E127ECDAWTPatterson et al., 2013
E127ECDEWTM,AgWTWTAgUnderwood et al., 2010
E128ECDAWTM,AgWTWTAgUnderwood et al., 2010
E128ECDAWTPatterson et al., 2013
E128ECDQWTM,AgWTWTAgUnderwood et al., 2010
E128ECDMWTDay et al., 2011
R1311.26bNWTC,AntWTWTEKoole et al., 2011
L1411.36bAWTC,AgWT67%cytYang et al., 2016
Y1451.40bAWTC,AgWT47%cytYang et al., 2016
Y1481.43bANDC,Ag26WTcytYang et al., 2016
Y1481.43bN15C,Ag8WTcytYang et al., 2016
Y1481.43bFNDC,Ag14WTcytYang et al., 2016
Y1481.43bF10C,Ant14WTcytYang et al., 2016
T1491.44bM60C,Ant14–33WTE & AntBeinborn et al., 2005
T1491.44bM*250C,Ant160<50%EEmax = NDKoole et al., 2011
For additional residue substiutions, see Koole et al., 2015
T1491.43bMNDC,Ag59WTcytYang et al., 2016
T1491.43bANDC,Ag82WTcytYang et al., 2016
T1491.43bSWTC,AgWTWTcytYang et al., 2016
Y1521.47bA30M,AntND7%AntCoopman et al., 2011
Y1521.47bHWTC,AgWTWTcytYang et al., 2016
S1551.50bAWTC,Ant1055%E, 48%AntΔLog τc = 0.75Wootten et al., 2013c
G168ICL1SWTC,AntWT<50%EKoole et al., 2011
F169ICL1†AWTC,AgWTAgWT cAMP 10−7 M GLP-1Mathi et al., 1997
R170ICL1†AWTC,AgWTAgWT cAMP 10−7 M GLP-1Mathi et al., 1997
H171ICL1†AWTC,AgWTAgWT cAMP 10−7 M GLP-1Mathi et al., 1997
L172ICL1†AWTC,Ag35%AgWT cAMP 10−7 M GLP-1Mathi et al., 1997
H173ICL1†AWTC,Ag48%AgWT cAMP 10−7 M GLP-1Mathi et al., 1997
C174ICL1†AWTC,Ag45%Ag37% cAMP 10−7 M GLP-1Mathi et al., 1997
C174ICL1A6Underwood et al., 2013
C174ICL1S7Underwood et al., 2013
T1752.45b†AWTC,Ag57%AgWT cAMP 10−7 M GLP-1Mathi et al., 1997
R1762.46b†AWTC,Ag13WTAg26% cAMP 10−7 M GLP-1Mathi et al., 1997
N1772.47b†AWTC,Ag22%Ag43% cAMP 10−7 M GLP-1Mathi et al., 1997
H1802.50b†R21C,AgWTmicHeller et al., 1996
H1802.50bANDC,Ant1218%E, NDAntΔLog τc = 0.86Wootten et al., 2013c
N1822.52b†AWTC,Ag24%Ag“36% of WT” cAMPXiao et al., 2000
S1862.56bAWTC,AntWTWTE,AntWootten et al., 2013c
F1872.57bANDC,AgND5%cytYang et al., 2016
R1902.60b†A>20C,Ag21%Ag“27% of WT” cAMPXiao et al., 2000
R1902.60bA32M,Ant2707%AntCoopman et al., 2011
R1902.60bA20C,Ant3453%E, 44AntΔLog τc = 0.53Wootten et al., 2013c
R1902.60bANDC,AgNDWTcytYang et al., 2016
R1902.60bKNDC,Ag17WTcytYang et al., 2016
R1902.60bK32C,Ant17WTcytYang et al., 2016
L1922.62bSWTUnderwood et al., 2011
L1922.62bSWTC,AgWTWTcytYang et al., 2016
V1942.64bAWTC,AgWTWTcytYang et al., 2016
F1952.65bLWT59%AgUnderwood et al., 2011
I1962.66b†SWTC,AgNDMoon et al., 2012
K1972.67bA28M,Ant63057%AntCoopman et al., 2011
K1972.67b†A5C,Ag30%Ag“25% of WT” cAMPXiao et al., 2000
K1972.67bANDC,AgND51%cytYang et al., 2016
K1972.67bINDC,AgND51%cytYang et al., 2016
K1972.67bI28C,AntND51%cytYang et al., 2016
K1972.67bQNDC,AgNDWTcytYang et al., 2016
K1972.67bRNDC,Ag23WTcytYang et al., 2016
D1982.68b†A10C,Ag16%Ag“45% of WT” cAMPXiao et al., 2000
D1982.68b†A63M,Ant44WTAntLópez de Maturana and Donnelly, 2002
D1982.68bA43M,Ant97766%AntCoopman et al., 2011
D1982.68bANDC,AgNDWTcytYang et al., 2016
D1982.68b†NWTM,AgLópez de Maturana and Donnelly, 2002
D1982.68bNNDC,Ag89WTcytYang et al., 2016
D1982.68bENDC,Ag434WTcytYang et al., 2016
D1982.68bE58C,Ant434WTcytYang et al., 2016
A200-L201†V/AWTM,AgWTLópez de Maturana et al., 2004
L2012.68bANDC,AgNDWTcytYang et al., 2016
K202ECL1†AWTC,Ag45%Ag“71% of WT” cAMPXiao et al., 2000
K202/W203†A/AWTM,AgWTLópez de Maturana et al., 2004
W203ECL1TWTC,AgWTWTcytYang et al., 2016
M204/Y205†A/A37M,Ant5128%AntLópez de Maturana et al., 2004
M204/Y205†V/A23M,Ag32WTAntLópez de Maturana et al., 2004
M204/Y205†A/V29M,Ag87WTAntLópez de Maturana et al., 2004
M204ECL1†AWTM,AgWT44%AntLópez de Maturana et al., 2004
M204ECL1ANDC,Ag334WTcytYang et al., 2016
M204ECL1RNDC,Ag93WTcytYang et al., 2016
Y205ECL1†AWTM,AgWTWTAntLópez de Maturana et al., 2004
Y205ECL1ANDC,Ag62WTcytYang et al., 2016
S206/T207†A/AWTM,AgWTLópez de Maturana et al., 2004
A208/A209†V/VWTM,AgWTLópez de Maturana et al., 2004
Q210Q211†A/AWTM,AgWTLópez de Maturana et al., 2004
Q211ECL1DWTC,AgWTWTcytYang et al., 2016
Q211ECL1RWTC,AgWTWTcytYang et al., 2016
H212ECL1†AWTC,AgWTAg“WT cAMP”Xiao et al., 2000
H212ECL1AWTC,AgWTWTcytYang et al., 2016
H212/Q213†A/AWTM,AgWTLópez de Maturana et al., 2004
D215ECL1†AWTC,Ag51%Ag“57% of WT” cAMPXiao et al., 2000
W214ECL1VWTC,AgWTWTcytYang et al., 2016
W214/D215†A/AWTM,AgWTLópez de Maturana et al., 2004
G216/L217†A/AWTM,AgWTLópez de Maturana et al., 2004
L217ECL1AWTC,AgWTWTcytYang et al., 2016
L218/S219†A/AWTM,AgWTLópez de Maturana et al., 2004
Y220/Q221†A/AWTM,AgWTLópez de Maturana et al., 2004
Y220ECL1DNDC,Ag105WTcytYang et al., 2016
D2223.25b†AWTC,AgWTAg“82% of WT” cAMPXiao et al., 2000
D222/S223†A/AWTM,AgWTLópez de Maturana et al., 2004
L224/G225†A/AWTM,AgWTLópez de Maturana et al., 2004
C2263.29b*†A25M,Ant3865%AntMann et al., 2010a
C2263.29bA>90Underwood et al., 2013
R2273.30b†A>20C,Ag31%Ag“90% WT” cAMPXiao et al., 2000
R227/L228†A/AWTM,AgWTLópez de Maturana et al., 2004
V229/F230†A/AWTM,AgWTLópez de Maturana et al., 2004
L232/M233†V/T10C,Ag100Moon et al., 2012
M2333.36bANDC,Ag70WTcytYang et al., 2016
M2333.36bA16C,Ant70WTcytYang et al., 2016
M2333.36bTNDC,Ag62WTcytYang et al., 2016
M2333.36bFWTC,AgWTWTcytYang et al., 2016
Q2343.37bA13M,Ant4527%AntCoopman et al., 2011
Q2343.37bANDC,Ag15135%cytYang et al., 2016
Q2343.37bNWTC,AgWTWTcytYang et al., 2016
Q2343.37bENDC,Ag2969%cytYang et al., 2016
Q2343.37bE17C,Ant2969%cytYang et al., 2016
Y2353.38bA24M,Ant2312%AntCoopman et al., 2011
C2363.39bAWTUnderwood et al., 2013
N2403.43b†A>20C,Ag14%Ag“8% WT” cAMPXiao et al., 2000
N2403.43bAWTC,Ant7WTE,AntΔLog τc = 0.67Wootten et al., 2013c
N2403.43bQWTC,AntWTWTE,AntWootten et al., 2016
N240/Q394A/AWTC,AntWT71%E,AntΔLog τc = 0.70Wootten et al., 2016
N240/Q394Q/N5C,AntWT71%E,AntWootten et al., 2016
Y2413.44bAWT42%AgUnderwood et al., 2011
Y2413.44bAWTC,AgWTWTcytYang et al., 2016
E2473.50bAWTC,Ag64%Ag“39% WT” cAMPXiao et al., 2000
E2473.50bANDC,Ant1418%E, NDAntΔLog τc = 0.99Wootten et al., 2013c
F260ICL2LWTC,AntWT<50%EKoole et al., 2011
E262ICL2†AWTC,AgWTAgWT cAMP 10−7 M GLP-1Mathi et al., 1997
Q263ICL2†AWTC,AgWTAgWT cAMP 10−7 M GLP-1Mathi et al., 1997
R264ICL2†AWTC,AgWTAgWT cAMP 10−7 M GLP-1Mathi et al., 1997
I265ICL2†AWTC,AgWTAgWT cAMP 10−7 M GLP-1Mathi et al., 1997
F2664.42b†AWTC,AgWTAgWT cAMP 10−7 M GLP-1Mathi et al., 1997
K2674.43b†AWTC,AgWTAgWT cAMP 10−7 M GLP-1Mathi et al., 1997
L2684.44b†AWTC,AgWTAgWT cAMP 10−7 M GLP-1Mathi et al., 1997
L2784.54bMWTUnderwood et al., 2011
W2844.60bA32M,Ant134934%AntCoopman et al., 2011
G2854.61bAWTC,AntWTWTEKoole et al., 2012a
I2864.62bAWTC,AntWTWTEKoole et al., 2012a
V2874.63bAWTC,AntWTWTEKoole et al., 2012a
I286/V287A/AWT85% SBM,AgDods and Donnelly, 2015
K2884.64bA126C,AntNDWTEKoole et al., 2012a
K2884.64bA23M,Ant5732WTAntΔLog τc = 1.39Dods and Donnelly, 2015
K2884.64b†A79M,Ant251Al-Sabah and Donnelly, 2003b
K2884.64b†L63M,Ant79Al-Sabah and Donnelly, 2003b
K2884.64bLNDC,AgND70%cytYang et al., 2016
K2884.64b†RWTM,AgWTAl-Sabah and Donnelly, 2003b
K288/Y289A, A218828% SBM,AgDods and Donnelly, 2015
Y2894.65bAWTC,AntWTWTEKoole et al., 2012a
Y2894.65bAWTM,AntWT20%AntDods and Donnelly, 2015
L2904.66bAWTC,AntWTWTEKoole et al., 2012a
Y2914.67bAWTC,AntWTWTEKoole et al., 2012a
L290/Y291†A/AWTM,AgWTMann et al., 2010a
L290-Y291A/AWT99% SBM,AgDods and Donnelly, 2015
E292ECL2A100C,Ant126WTEΔLog τc = 0.57Koole et al., 2012a
E292ECL2ANDC,Ag3339%cytYang et al., 2016
D293ECL2A25C,Ant1662%EKoole et al., 2012a
E292/D293†A/A8M,Ag79Mann et al., 2010a
E292/D293A/A2575% SBM,AgDods and Donnelly, 2015
E294ECL2AWTC,AntWTWTEΔLog τc = 0.65Koole et al., 2012a
G295ECL2AWTC,AntWTWTEKoole et al., 2012a
E294-G295†A/AWTM,AgWTMann et al., 2010a
E294-G295A/AWT97% SB M,AgDods and Donnelly, 2015
C296ECL2*†A18M,AntWT23%AntMann et al., 2010a
C296ECL2A13C,Ant12660EKoole et al., 2012a
C296ECL2SNDC,Ag96WTcytYang et al., 2016
W297ECL2A63C,Ant316WTEΔLog τc = 1.00Koole et al., 2012a
W297ECL2ANDC,AgNDWTcytYang et al., 2016
W297ECL2HNDC,Ag5040%cytYang et al., 2016
T298ECL2AWTC,AntWTWTEKoole et al., 2012a
W297/T298†A/A100M,Ant50Mann et al., 2010a;
Donnelly, 2012
W297/T298A/A2257% SBM,AgDods and Donnelly, 2015
R299ECL2A32C,Ant85WTEKoole et al., 2012a
R299ECL2AWTM,AntWT40%AntΔLog τc = 0.60Dods and Donnelly, 2015
R299ECL2SNDC,Ag43WTcytYang et al., 2016
N300ECL2A126C,Ant501WTEΔLog τc = 0.80Koole et al., 2012a
N300ECL2A36M,Ant10418%AntDods and Donnelly, 2015
N300ECL2ANDC,AgND16%cytYang et al., 2016
R299/N300†A/A25M,Ant>3000Mann et al., 2010a;
Donnelly, 2012
R299/N300A/A33141% SBM,AgDods and Donnelly, 2015
S301ECL2AWTC,AntWT63%EKoole et al., 2012a
N302ECL2A25C,Ant16WTEΔLog τc = 0.53Koole et al., 2012a
S301/N302†A/AWTM,AgWTMann et al., 2010a
S301/N302A/AWT86% SBM,AgDods and Donnelly, 2015
N302/M303†V/KWTC,Ag10Moon et al., 2012
M303ECL2AWTC,AntWTWTEKoole et al., 2012a
N304ECL2AWTC,AntWT70%EΔLog τc = 0.74Koole et al., 2012a
N304ECL2AWTC,AgWTWTcytYang et al., 2016
M303/N304†A/AWTM,AgWTMann et al., 2010a
M303/N304A/AWT91% SBM,AgDods and Donnelly, 2015
Y3055.35bA79C,Ant4052%EKoole et al., 2012a
Y3055.35bAWTM,AntWT22%AntDods and Donnelly, 2015
W3065.36bANDC,AntNDNDNo receptor expressionKoole et al., 2012a
W3065.36A109M,Ant20641%AntDods and Donnelly, 2015
W3065.36ANDC,AgNDWTcytYang et al., 2016
†Y305/W306†A/A316M,Ant50Mann et al., 2010a;
Donnelly, 2012
Y305/W306A/A26360% SBM,AgDods and Donnelly, 2015
L3075.37bA13C,Ant2547%EKoole et al., 2012a
L3075.37bAWT87% SBM,AgDods and Donnelly, 2015
I3085.38bAWT78% SBM,AgDods and Donnelly, 2015
L307/I308†A/A251M,Ant6Mann et al., 2010a;
Donnelly 2012
I3095.39bAWTM,AntWTWTAntDods and Donnelly, 2015
R3105.40bA10M,Ant125917%AntCoopman et al., 2011
R3105.40bAWTM,Ant129019%AntΔLog τc = 0.75Dods and Donnelly, 2015
I309/R310†A/A50M,Ant>3000Mann et al., 2010a;
Donnelly, 2012
I309/R310A/A13,49013% SBM,AgDods and Donnelly, 2015
L311/P312A/AWT91% SBM,AgDods and Donnelly, 2015
A3165.46bTWTC,AntWT<25%EKoole et al., 2011
N3205.50bA18C,Ant10WTE,AntΔLog τc = 0.50Wootten et al., 2013c
F3215.51b†AWTC,AgWTAgWT cAMP 10−7 M GLP-1Mathi et al., 1997
L3225.52b†AWTC,AgWTAgWT cAMP 10−7 M GLP-1Mathi et al., 1997
I3235.53b†AWTC,Ag35%AntWT cAMP 10−7 M GLP-1Mathi et al., 1997
F3245.54b†AWTC,AgWTAgWT cAMP 10−7 M GLP-1Mathi et al., 1997
I325/F326†A/AWTC,AgWTAgWT cAMP 10−7 M GLP-1Mathi et al., 1997
V3275.57b†AWTC,Ag15WTAg42% cAMP 10−7 M GLP-1Mathi et al., 1997
I3285.58b†AWTC,Ag9WTAnt39% cAMP 10−7 M GLP-1Mathi et al., 1997
C3295.59b†AWTC,AgWTAntWT cAMP 10−7 M GLP-1Mathi et al., 1997
I3305.60bAWTC,AgWTAgWT cAMP 10−7 M GLP-1Mathi et al., 1997
V3315.61b†AWTC,Ag14WTAg45% cAMP 10−7 M GLP-1Mathi et al., 1997
I3325.62b†AWTC,AgWTAgWT cAMP 10−7 M GLP-1Mathi et al., 1997
A3335.63b†LWTC,AgWTAgWT cAMP 10−7 M GLP-1Mathi et al., 1997
S3335.63bCWTC,AntWT<50%EFor additional residue substiutions, see Koole et al., 2015Koole et al., 2011
K3345.64b†AWTC,AgWTAg28% cAMP 10−7 M GLP-1Takhar et al., 1996;
Mathi et al., 1997
L3355.65b†AWTC,AgWTAgWT cAMP 10−7 M GLP-1Takhar et al., 1996;
Mathi et al., 1997
K3365.66b†LWTC,AgWTAgWT cAMP 10−7 M GLP-1Takhar et al., 1996;
Mathi et al., 1997
K334/K351DeletionsWTC,AgAg See paper for detailsTakhar et al., 1996
C3476.36bAWTUnderwood et al., 2013
R3486.37b†G12C,AgNDWTmicHeller et al., 1996
R3486.37b†AWTC,AgWTAgWT cAMP 10−7 M GLP-1Takhar et al., 1996
L3496.38b†AWTC,Ag76%AgWT cAMP 10−7 M GLP-1Takhar et al., 1996
A-3506.39b†ENDC,Ag<10%Ag5% cAMP 10−7 M GLP-1Takhar et al., 1996
A-3506.39b†KWTC,Ag21%Ag2% cAMP 10−7 M GLP-1Takhar et al., 1996
K3516.40b†AWTC,AgWTAgWT cAMP 10−7 M GLP-1Takhar et al., 1996
T3536.42bANDC,Ant2230%E, NDAntΔLog τc = 0.84Wootten et al., 2013c
H3636.52bA98M,AntND24%AntCoopman et al., 2011
H3636.52bA23C,Ant459%E, 53%AntΔLog τc = 1.71Wootten et al., 2013c
E3646.53bA58M,Ant1542%AntCoopman et al., 2011
E3646.53bA25C,Ant51%E,AntΔLog τc = 0.66Wootten et al., 2016
E3646.53bANDC,AgND6%cytYang et al., 2016
E3646.53bQWTC,AgWT42%cytYang et al., 2016
E3646.53bQ0.2C,AntWT42%cytYang et al., 2016
E364/E387N/QNDC,AgNDWTcytYang et al., 2016
E3646.53bYWTC,AgWTWTcytYang et al., 2016
E3646.53bDWTC,AgWT53%cytYang et al., 2016
F3676.56bANDC,Ag72WTcytYang et al., 2016
F3676.56bA32C,Ant72WTcytYang et al., 2016
F3676.56bINDC,Ag20WTcytYang et al., 2016
F3676.56bH7C,Ag131WTcytYang et al., 2016
M371ECL3AWT M,AntWT54%AntDods and Donnelly, 2015
D372ECL3AWT M,Ant5913%AntDods and Donnelly, 2015
E373ECL3AWTM,AntWT28%AntDods and Donnelly, 2015
H374ECL3AWTM,AntWT22%AntDods and Donnelly, 2015
H374ECL3AWTC,AgWTWTcytYang et al., 2016
A-375ECL3A10M,AntWTWTAntDods and Donnelly, 2015
R376ECL3GWTM,AntWTWTAntDods and Donnelly, 2015
R376ECL3QWTC,AgWTWTcytYang et al., 2016
G377ECL3AWTM,AntWT19%AntDods and Donnelly, 2015
T3787.32bAWTM,AntWT12%AntDods and Donnelly, 2015
L3797.33bR12C,Ag141WTAgMoon et al., 2015
L3797.33bE11C,Ag165WTAgMoon et al., 2015
L3797.33bAWTM,AntWT31%AntDods and Donnelly, 2015
R3807.34bD21C,Ag1853WTAgMoon et al., 2015
R3807.34bG4C,Ag40WTAgMoon et al., 2015
R3807.34bA128M,Ant26368%AntDods and Donnelly, 2015
R3807.34bQNDC,AgNDWTcytYang et al., 2016
F3817.35bRWT C,AgWTWTAgMoon et al., 2015
F3817.35bE>200C,Ag234WTAgMoon et al., 2015
F3817.35bAWTM,AntWT16%AntDods and Donnelly, 2015
F3817.35bSWTC,AgWTWTcytYang et al., 2016
I3827.36bAWTM,AntWT23%AntDods and Donnelly, 2015
K3837.37bAWTM,Ant56WTAntΔLog τc = 1.18Dods and Donnelly, 2015
L3847.38bAWTM,AntWTWTAntDods and Donnelly, 2015
L3847.38bANDC,Ag41WTcytYang et al., 2016
L3847.38bA48C,Ant41WTcytYang et al., 2016
L3847.38bVNDC,Ag16WTcytYang et al., 2016
F3857.40bAWTM,AntWTWTAntDods and Donnelly, 2015
T3867.41bAWTM,AntWT18%AntDods and Donnelly, 2015
E3877.42bAWTM,AntWT43%AntΔLog τc = 0.52Dods and Donnelly, 2015
E3877.42bAWTM,AntWTWTAntCoopman et al., 2011
E3877.42bD13C,Ag10WTcytYang et al., 2016
E3877.42bD12C,Ant10WTcytYang et al., 2016
E3877.42bNWTC,AgWTWTcytYang et al., 2016
L3887.43bANDC,Ag208WTcytYang et al., 2016
L3887.43bI5C,Ag81WTcytYang et al., 2016
L3887.43bFWTC,AgWTWTcytYang et al., 2016
T3917.44bAWTM,AntWT64%M,AntCoopman et al., 2011
T3917.44bAWTWTAgUnderwood et al., 2011
S3927.47bAWTC,AntWTWTE, AntWootten et al., 2013c
Q3947.49bAWTC,AntWTWTE, AntWootten et al., 2013c
Q3947.49bNWTC,AntWTE,AntWootten et al., 2016
M3977.52bLWTC,AgWTDong et al., 2012
Y4027.57bANDC,Ant1021%E, NDAntΔLog τc = 1.59Wootten et al., 2013c
C4037.58bA5.4Underwood et al., 2013
N4067.61bAWTC,AntWTWTE,AntWootten et al., 2013c
R421CTTQWTC,AntWT<50%EKoole et al., 2011
C438 CTTAWTUnderwood et al., 2013
C458 CTTAWTUnderwood et al., 2013
C462 CTTAWTUnderwood et al., 2013

  • CTT, C-terminal tail; SB, specific binding of radiolabeled ligand; WB, Western blotting.

  • ↵† Note that potency changes can be due to changes in affinity, efficacy, and/or cell surface expression, and hence should be interpreted with caution, especially when either the affinity and/or expression levels are not known.

  • ↵* Also included in double mutations.