Table 1. Summary of the available... | Rockefeller University Press

Table 1.

Summary of the available crystal structures of the glutamate transporter homologues

Glt/EAAT1^{^a}	Ligand	Ions^{^b}	X-link	State	PDB ID	Resolution	Space group	Completeness^{^c}	Clash score^{^d}	R_work/R_free^{^e}	Comments, new features	Mutations	Reference
						Å		%		%
Ph	Not assigned			OFC occluded	1XFH	3.5	P 6₁	97.1 (n.r.)	21	*29.0/30.9*	Homotrimer, bowl shape, overall fold	7H mutations: D37H, K40H, K125H, K132H, K223H, K264H, E368H	Yernool et al., 2004
Ph	l-Asp			OFC occluded	2NWL	2.96	P 6₁	*69.3 (8.8)*	5	23.6/26.5	Substrate-binding site	7H mutations	Boudker et al., 2007
Ph	l-Asp	Tl1, Tl2		OFC occluded	2NWX	3.29	P 6₁	*69.2 (12.1)*	15	26.3/28.6	Na1 and Na2 binding sites	7H mutations	Boudker et al., 2007
Ph	TBOA			OFC open	2NWW	3.2	P 6₁	*74.8 (15.5)*	8	*24.1/26.0*	Open conformation of HP2; *modeling of TBOA binding*	7H mutations	Boudker et al., 2007
Ph	l-Asp	Na1, Na2, Hg	HgCl₂	IFC occluded	3KBC	3.51	C 2 2 2₁	97.2 (84.5)	*108*	*26.7/27.0*	IFC, elevator mechanism	7H mutations, K55C, C321A, A364C	Reyes et al., 2009
Ph	l-Asp	Na1, Na2; Hg	HgCl₂	IFC occluded	3V8F	3.8	C 1 2 1	99.5 (97.6)	26	*24.3/25.5*	IFC, different mutant	7H mutations, V216C, C321A, M385C	Verdon and Boudker, 2012
Ph	l-Asp	Na1, Na2	HgCl₂	iOFC occluded	3V8G	4.66	C 1 2 1	*73.1 (11.2)*	14	25.5/29.4	*Intermediate OFC*	7H mutations, V198C, C321A, A380C	Verdon and Boudker, 2012
Ph	l-Asp	Na1, Na2; Hg	HgCl₂	OFC occluded	4IZM	4.5	P 6₁	99.7 (99.1)	12	25.0/29.9		7H mutations, L66C, S300C, C321A	Reyes et al., 2013
Tk				OFC occluded	4KY0	3.0	P 3₂ 2 1	99.8 (99.8)	13	21.2/26.6	OFC apo protein without Na	-	Jensen et al., 2013
Ph		Tl1, Tl2; Hg	HgCl₂	IFC occluded	4P6H	4.08	C 2 2 2₁	*67.4 (6.4)*	39	25.8/29.6	IFC apo protein with Tl	7H mutations, K55C, C321A, A364C, E418T	Verdon et al., 2014
Ph		Tl^Ct, Tl2; Hg	HgCl₂	IFC occluded	4P1A	3.75	C 2 2 2₁	99.7 (99.7)	24	23.0/25.7	*New cation site*	7H mutations, K55C, C321A, A364C	Verdon et al., 2014
Ph		Hg	HgCl₂	IFC occluded	4P19	3.25	C 2 2 2₁	99.1 (91.9)	23	22.2/25.8	IFC apo protein without Na	7H mutations, K55C, C321A, A364C	Verdon et al., 2014
Ph		Hg	HgCl₂	IFC occluded	4P3J	3.5	C 2 2 2₁	95.5 (93.2)	12	*26.3/27.8*		7H mutations, K55C, C321A, A364C	Verdon et al., 2014
Ph				OFC, occluded	4OYE	4.0	P 1 2₁ 1	*70.3 (9.3)*	13	*24.9/26.6*		7H mutations, R397A	Verdon et al., 2014
Ph		*Na1*		OFC occluded, tip open	4OYF	3.41	P 3₁	88.7 (12.2)	26	*28.4/29.3*	OFC apo protein *with Na*	7H mutations, R397A	Verdon et al., 2014
Ph	l-Asp	Na1, Na2		OFC occluded	4OYG/5CFY	3.5	P 3₁	97.1 (93.7)	24	24.9/29.4		7H mutations, R397A	Verdon et al., 2014
Ph	l-Asp	Na1, Na2		iIFC occluded	4X2S	4.21	P 6₅ 2 2	83.2 (18.3)	10	27.8/31.4	IFC occluded, *locked and unlocked*	7H mutations, R276S, C321A, M395R, E418T	Akyuz et al., 2015
Tk				OFC occluded	5DWY	2.7	P 3₂ 2 1	*79.0 (17.9)*	5	19.8/23.7	Improved 4KY0		Guskov et al., 2016
Tk	l-Asp	Na1, Na2, Na3		OFC occluded	5E9S	2.8	P 3₂ 2 1	97.4 (97.0)	8	21.3/24.3	Na3 site; loop 3–4; Na/l-Asp coupling mechanism		Guskov et al., 2016
Hs	l-Asp, UCPH₁₀₁	Na2		OFC occluded	5LLM	3.25	P 6₃	80.2 (39.1)	4	21.9/24.0	Glt_Ph-like fold, allosteric inhibition by UCPH₁₀₁	73 mutations: R23S, Y44F, F46R, F50L, V51L, T56L, V60L, T62V, I63V, T67L, R72P, M73L, Y75P, S82A, Q93K, V96I, I101V, V105I, M108L, A110S, S113A, K118R, M119L, T129S, I137L, I141L, I143L, N155T, S175C, N204T, A223I, C232V, V236A, I237L, N239K, K241G, A246L, R248V, E249D, D252N, I258T, R260K, V264I, V271L, M287L, G288E, I290L, A295G, T298M, L306V, A309G, V310L, L316I, V320I, W326F, G330A, L332I, V366I, L388V, F399Y, N402D, S437A, F454L, L458F, T461M, T462V, S468A, H480K, K483E, N484K, R485Q, V487A, M489L	Canul-Tec et al., 2017
Hs	l-Asp, UCPH₁₀₁	Na2		OFC occluded	5LM4	3.10	P 6₃	*75.9 (31.7)*	4	21.7/25.9	Nearly identical to 5LLM	73 mutations, K149A, M231I, F235I	Canul-Tec et al., 2017
Hs	l-Asp	Na2		OFC, occluded	5LLU	3.32	P 6₃	80.4 (40.1)	5	20.9/25.3	No inhibitors bound	73 mutations, M231I, F235I	Canul-Tec et al., 2017
Hs	UCPH₁₀₁, TBOA_TFB			OFC open	5MJU	3.71	P 6₃	80.3 (40.5)	3	22.7/25.4	Similar to 5LLM but with HP2 tip open, TBOA_TFB binding	73 mutations	Canul-Tec et al., 2017

Glt/EAAT1^{^a}	Ligand	Ions^{^b}	X-link	State	PDB ID	Resolution	Space group	Completeness^{^c}	Clash score^{^d}	R_work/R_free^{^e}	Comments, new features	Mutations	Reference
						Å		%		%
Ph	Not assigned			OFC occluded	1XFH	3.5	P 6₁	97.1 (n.r.)	21	*29.0/30.9*	Homotrimer, bowl shape, overall fold	7H mutations: D37H, K40H, K125H, K132H, K223H, K264H, E368H	Yernool et al., 2004
Ph	l-Asp			OFC occluded	2NWL	2.96	P 6₁	*69.3 (8.8)*	5	23.6/26.5	Substrate-binding site	7H mutations	Boudker et al., 2007
Ph	l-Asp	Tl1, Tl2		OFC occluded	2NWX	3.29	P 6₁	*69.2 (12.1)*	15	26.3/28.6	Na1 and Na2 binding sites	7H mutations	Boudker et al., 2007
Ph	TBOA			OFC open	2NWW	3.2	P 6₁	*74.8 (15.5)*	8	*24.1/26.0*	Open conformation of HP2; *modeling of TBOA binding*	7H mutations	Boudker et al., 2007
Ph	l-Asp	Na1, Na2, Hg	HgCl₂	IFC occluded	3KBC	3.51	C 2 2 2₁	97.2 (84.5)	*108*	*26.7/27.0*	IFC, elevator mechanism	7H mutations, K55C, C321A, A364C	Reyes et al., 2009
Ph	l-Asp	Na1, Na2; Hg	HgCl₂	IFC occluded	3V8F	3.8	C 1 2 1	99.5 (97.6)	26	*24.3/25.5*	IFC, different mutant	7H mutations, V216C, C321A, M385C	Verdon and Boudker, 2012
Ph	l-Asp	Na1, Na2	HgCl₂	iOFC occluded	3V8G	4.66	C 1 2 1	*73.1 (11.2)*	14	25.5/29.4	*Intermediate OFC*	7H mutations, V198C, C321A, A380C	Verdon and Boudker, 2012
Ph	l-Asp	Na1, Na2; Hg	HgCl₂	OFC occluded	4IZM	4.5	P 6₁	99.7 (99.1)	12	25.0/29.9		7H mutations, L66C, S300C, C321A	Reyes et al., 2013
Tk				OFC occluded	4KY0	3.0	P 3₂ 2 1	99.8 (99.8)	13	21.2/26.6	OFC apo protein without Na	-	Jensen et al., 2013
Ph		Tl1, Tl2; Hg	HgCl₂	IFC occluded	4P6H	4.08	C 2 2 2₁	*67.4 (6.4)*	39	25.8/29.6	IFC apo protein with Tl	7H mutations, K55C, C321A, A364C, E418T	Verdon et al., 2014
Ph		Tl^Ct, Tl2; Hg	HgCl₂	IFC occluded	4P1A	3.75	C 2 2 2₁	99.7 (99.7)	24	23.0/25.7	*New cation site*	7H mutations, K55C, C321A, A364C	Verdon et al., 2014
Ph		Hg	HgCl₂	IFC occluded	4P19	3.25	C 2 2 2₁	99.1 (91.9)	23	22.2/25.8	IFC apo protein without Na	7H mutations, K55C, C321A, A364C	Verdon et al., 2014
Ph		Hg	HgCl₂	IFC occluded	4P3J	3.5	C 2 2 2₁	95.5 (93.2)	12	*26.3/27.8*		7H mutations, K55C, C321A, A364C	Verdon et al., 2014
Ph				OFC, occluded	4OYE	4.0	P 1 2₁ 1	*70.3 (9.3)*	13	*24.9/26.6*		7H mutations, R397A	Verdon et al., 2014
Ph		*Na1*		OFC occluded, tip open	4OYF	3.41	P 3₁	88.7 (12.2)	26	*28.4/29.3*	OFC apo protein *with Na*	7H mutations, R397A	Verdon et al., 2014
Ph	l-Asp	Na1, Na2		OFC occluded	4OYG/5CFY	3.5	P 3₁	97.1 (93.7)	24	24.9/29.4		7H mutations, R397A	Verdon et al., 2014
Ph	l-Asp	Na1, Na2		iIFC occluded	4X2S	4.21	P 6₅ 2 2	83.2 (18.3)	10	27.8/31.4	IFC occluded, *locked and unlocked*	7H mutations, R276S, C321A, M395R, E418T	Akyuz et al., 2015
Tk				OFC occluded	5DWY	2.7	P 3₂ 2 1	*79.0 (17.9)*	5	19.8/23.7	Improved 4KY0		Guskov et al., 2016
Tk	l-Asp	Na1, Na2, Na3		OFC occluded	5E9S	2.8	P 3₂ 2 1	97.4 (97.0)	8	21.3/24.3	Na3 site; loop 3–4; Na/l-Asp coupling mechanism		Guskov et al., 2016
Hs	l-Asp, UCPH₁₀₁	Na2		OFC occluded	5LLM	3.25	P 6₃	80.2 (39.1)	4	21.9/24.0	Glt_Ph-like fold, allosteric inhibition by UCPH₁₀₁	73 mutations: R23S, Y44F, F46R, F50L, V51L, T56L, V60L, T62V, I63V, T67L, R72P, M73L, Y75P, S82A, Q93K, V96I, I101V, V105I, M108L, A110S, S113A, K118R, M119L, T129S, I137L, I141L, I143L, N155T, S175C, N204T, A223I, C232V, V236A, I237L, N239K, K241G, A246L, R248V, E249D, D252N, I258T, R260K, V264I, V271L, M287L, G288E, I290L, A295G, T298M, L306V, A309G, V310L, L316I, V320I, W326F, G330A, L332I, V366I, L388V, F399Y, N402D, S437A, F454L, L458F, T461M, T462V, S468A, H480K, K483E, N484K, R485Q, V487A, M489L	Canul-Tec et al., 2017
Hs	l-Asp, UCPH₁₀₁	Na2		OFC occluded	5LM4	3.10	P 6₃	*75.9 (31.7)*	4	21.7/25.9	Nearly identical to 5LLM	73 mutations, K149A, M231I, F235I	Canul-Tec et al., 2017
Hs	l-Asp	Na2		OFC, occluded	5LLU	3.32	P 6₃	80.4 (40.1)	5	20.9/25.3	No inhibitors bound	73 mutations, M231I, F235I	Canul-Tec et al., 2017
Hs	UCPH₁₀₁, TBOA_TFB			OFC open	5MJU	3.71	P 6₃	80.3 (40.5)	3	22.7/25.4	Similar to 5LLM but with HP2 tip open, TBOA_TFB binding	73 mutations	Canul-Tec et al., 2017

Indicators of low structure quality and uncertain features are shown in bold italic style.

Ph, Pyrococcus horikoshii (Glt_Ph); Tk, Thermococcus kodakarensis (Glt_Tk); Hs, Homo sapiens (EAAT1).

Na1, Na2, Na3, Tl1, Tl2, sodium or thallium ions included in the model in the corresponding sodium sites; Tl^Ct, thallium ion in the proposed cation-binding site.

Overall completeness and completeness for the highest-resolution shell (in parentheses) as given in PDB data refinement statistics; n.r., not reported.

Clash score value is given according to a global validation metrics of the PDB entry. It is calculated from the pairs of atoms in the model that are unusually close to each other (Chen et al., 2010) and expressed as a number of serious clashes (>0.4 Å) per thousand atoms. Values >20 are considered problematic.

R_free is typically ∼4–7% higher than R_work. The extremely small R_free − R_wor_k difference might indicate a compromised test data set (Wlodawer et al., 2008; Wlodawer, 2017).

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