Table 1. Summary of the available crystal structures of the glutamate transporter homologues
Glt/EAAT1aLigandIonsbX-linkStatePDB IDResolutionSpace groupCompletenesscClash scoredRwork/RfreeeComments, new featuresMutationsReference
Å%%
PhNot assignedOFC occluded1XFH3.5P 6197.1 (n.r.)2129.0/30.9Homotrimer, bowl shape, overall fold7H mutations: D37H, K40H, K125H, K132H, K223H, K264H, E368HYernool et al., 2004
Phl-AspOFC occluded2NWL2.96P 6169.3 (8.8)523.6/26.5Substrate-binding site7H mutationsBoudker et al., 2007
Phl-AspTl1, Tl2OFC occluded2NWX3.29P 6169.2 (12.1)1526.3/28.6Na1 and Na2 binding sites7H mutationsBoudker et al., 2007
PhTBOAOFC open2NWW3.2P 6174.8 (15.5)824.1/26.0Open conformation of HP2; modeling of TBOA binding7H mutationsBoudker et al., 2007
Phl-AspNa1, Na2, HgHgCl2IFC occluded3KBC3.51C 2 2 2197.2 (84.5)10826.7/27.0IFC, elevator mechanism7H mutations, K55C, C321A, A364CReyes et al., 2009
Phl-AspNa1, Na2; HgHgCl2IFC occluded3V8F3.8C 1 2 199.5 (97.6)2624.3/25.5IFC, different mutant7H mutations, V216C, C321A, M385CVerdon and Boudker, 2012
Phl-AspNa1, Na2HgCl2iOFC occluded3V8G4.66C 1 2 173.1 (11.2)1425.5/29.4Intermediate OFC7H mutations, V198C, C321A, A380CVerdon and Boudker, 2012
Phl-AspNa1, Na2; HgHgCl2OFC occluded4IZM4.5P 6199.7 (99.1)1225.0/29.97H mutations, L66C, S300C, C321AReyes et al., 2013
TkOFC occluded4KY03.0P 32 2 199.8 (99.8)1321.2/26.6OFC apo protein without Na-Jensen et al., 2013
PhTl1, Tl2; HgHgCl2IFC occluded4P6H4.08C 2 2 2167.4 (6.4)3925.8/29.6IFC apo protein with Tl7H mutations, K55C, C321A, A364C, E418TVerdon et al., 2014
PhTlCt, Tl2; HgHgCl2IFC occluded4P1A3.75C 2 2 2199.7 (99.7)2423.0/25.7New cation site7H mutations, K55C, C321A, A364CVerdon et al., 2014
PhHgHgCl2IFC occluded4P193.25C 2 2 2199.1 (91.9)2322.2/25.8IFC apo protein without Na7H mutations, K55C, C321A, A364CVerdon et al., 2014
PhHgHgCl2IFC occluded4P3J3.5C 2 2 2195.5 (93.2)1226.3/27.87H mutations, K55C, C321A, A364CVerdon et al., 2014
PhOFC, occluded4OYE4.0P 1 21 170.3 (9.3)1324.9/26.67H mutations, R397AVerdon et al., 2014
PhNa1OFC occluded, tip open4OYF3.41P 3188.7 (12.2)2628.4/29.3OFC apo protein with Na7H mutations, R397AVerdon et al., 2014
Phl-AspNa1, Na2OFC occluded4OYG/5CFY3.5P 3197.1 (93.7)2424.9/29.47H mutations, R397AVerdon et al., 2014
Phl-AspNa1, Na2iIFC occluded4X2S4.21P 65 2 283.2 (18.3)1027.8/31.4IFC occluded, locked and unlocked7H mutations, R276S, C321A, M395R, E418TAkyuz et al., 2015
TkOFC occluded5DWY2.7P 32 2 179.0 (17.9)519.8/23.7Improved 4KY0Guskov et al., 2016
Tkl-AspNa1, Na2, Na3OFC occluded5E9S2.8P 32 2 197.4 (97.0)821.3/24.3Na3 site; loop 3–4; Na/l-Asp coupling mechanismGuskov et al., 2016
Hsl-Asp, UCPH101Na2OFC occluded5LLM3.25P 6380.2 (39.1)421.9/24.0GltPh-like fold, allosteric inhibition by UCPH10173 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, M489LCanul-Tec et al., 2017
Hsl-Asp, UCPH101Na2OFC occluded5LM43.10P 6375.9 (31.7)421.7/25.9Nearly identical to 5LLM73 mutations, K149A, M231I, F235ICanul-Tec et al., 2017
Hsl-AspNa2OFC, occluded5LLU3.32P 6380.4 (40.1)520.9/25.3No inhibitors bound73 mutations, M231I, F235ICanul-Tec et al., 2017
HsUCPH101, TBOATFBOFC open5MJU3.71P 6380.3 (40.5)322.7/25.4Similar to 5LLM but with HP2 tip open, TBOATFB binding73 mutationsCanul-Tec et al., 2017
  • Indicators of low structure quality and uncertain features are shown in bold italic style.

  • a Ph, Pyrococcus horikoshii (GltPh); Tk, Thermococcus kodakarensis (GltTk); Hs, Homo sapiens (EAAT1).

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

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

  • d 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.

  • e Rfree is typically ∼4–7% higher than Rwork. The extremely small RfreeRwork difference might indicate a compromised test data set (Wlodawer et al., 2008; Wlodawer, 2017).