Supplementary Figure 3: Characteristics of the positively charged groove of vasohibins and inhibition of vasohibins by small molecules. | Nature Structural & Molecular Biology

Supplementary Figure 3: Characteristics of the positively charged groove of vasohibins and inhibition of vasohibins by small molecules.

From: Structural basis of tubulin detyrosination by the vasohibin–SVBP enzyme complex

Supplementary Figure 3

a–b, 14 conserved lysine and arginine residues (see also Supplementary Note) shape the positively charged groove of the V2c–SVBP (a) and V1c–SVBP (b) structures. c, Chemical structure of epoY that inhibits vasohibins with very good potency. d, Superimposition of the structures of V2c–SVBP (color coded as in Fig. 1a) and V2c–SVBP–epoY (wheat) in cartoon representation with the epoY shown in sticks representation. The rmsd of the two superimposed structures is 0.61 Å. e, Related to (d), walleye stereo view highlighting the covalent linkage between epoY and the catalytic residue C158 of V2c. f, Superimposition of the active site residues of V2c-SVBP (green) onto the ones of V2c–SVBP–epoY (wheat) in sticks representation. The red arrows highlight the conformational changes that residues experience upon ligand binding. g, Chemical structure of TPCK that inhibits vasohibins with very good potency. h, Superimposition of the structures of V2c–SVBP (color coded as in Fig. 1a) and V2c–SVBP–TPCK (wheat) in cartoon representation with the ligand TPCK shown in sticks. The rmsd is 0.43 Å. i, Superimposition of the active site residues of V2c–SVBP (green) onto the ones of V2c–SVBP–TPCK (wheat) in sticks representation. The red arrows highlight the conformational changes that residues experience upon ligand binding. j–l, Chemical structures of TLCK (j), E-64 (k) and parthenolide (l). The ligands TLCK, E-64 and parthenolide only show modest inhibitory activity against vasohibins. m, Zoom in view on the active site residues of the structure of carboxypeptidase A (CPA) in complex with a Gly-Tyr dipeptide (PDB ID 3CPA). Interacting residues of CPA (green) with the Gly-Tyr dipeptide (wheat) are shown in sticks representation. Both the catalytic residue E270 and the catalytic zinc atom are also highlighted, with the zinc-coordinating residues omitted for clarity.

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