Fig. 4
Conserved positively charged sulfate and citrate binding pocket in proximity to the metal site indicates the binding site for D-myo-inositol-3-phosphate. a Localization and coordination environment of two sulfate ions in the CDP-DAG bound M. tuberculosis PgsA1 at the active site. Black dashed lines indicate hydrogen bonds between the sulfate ions and protein residues. Red dashed lines denote sulfate ion proximity (in Å) to the catalytic aspartate and the metal site. b, c Structural overlay of sulfate ion binding site in the CDP-DAG-bound M. tuberculosis PgsA1 with citrate ion binding site in the Mn-citrate M. tuberculosis PgsA1 in both protein chains, A and B. Citrate-chelated metals are omitted for clarity. The citrate molecule, which binds in the same site as the sulfate ions, is shown in cyan. The second citrate found only in chain A is shown in silver sticks. d, e Two representative binding poses of D-myo-inositol-3-phosphate were selected from two preeminent molecular docking clusters. The top-scored binding pose, denoted #1 in the main text, is shown in yellow sticks; and the second potential binding pose, denoted #2, is shown in magenta sticks. Red dashed line denotes proximity of the D-myo-inositol-3-phosphate 1′ hydroxyl group and the catalytic aspartate. The sulfate ions of the M. tuberculosis PgsA1 structure are shown in gray sticks. Bound CDP-DAG is omitted for clarity. f The sulfates are bound to the positively charged pocket (blue) in the vicinity to the metal site and the catalytic aspartate. Surface potential is calculated using PyMOL 2.0.022. CDP-DAG is shown in cyan. Mg ion protruding through the surface representation is shown in green
