PvSUB1 homology 3D-model

Plasmodium vivax Subtilisin 1 (Genbank N° FJ536584) homology model generated by the modeling software Modeller and cited in Bastianelli et al, Plos One In press 2014)

Docking results.

<p>The red circles indicate the docking poses that have been selected for refinement.</p

Docking of PvSUB1 hexapeptide substrate into PvSUB1 catalytic groove.

<p>Blue: P4, Violet: P3, Yellow: P2, Red: P1, Cyan: P1′, Green: P2′.</p

Free energy decomposition.

<p>Blue: All atoms, Red: Side chain atoms, Green: Backbone atoms. The largest contribution to the free energy of binding comes from the main-chain contacts of residues P4, P3, P2 and P1. The highest contribution comes from the cysteine in P3 and its main-chain, accounting for −4.34 kcal/mol.</p

Catalytic site distances along MD simulations.

<p>Catalytic site distances along MD simulations.</p

EETI-II-sub docked to PvSUB1.

<p>Blue: P4, Violet: P3, Yellow: P2, Red: P1, Cyan: P1′.</p

Scoring mutations on P4 and P1.

<p><b>A:</b> mutants in position P4. The mutational profile of P4 shows that hydrophobic and bulky residues are preferred for this position. <b>B:</b> mutants in position P1. Position P1 instead prefers aromatic residues with polar groups (Tyr, Trp), glutamate and positively charged residues (Lys, Arg).</p

Sequence and inhibitory activity of EETI-II mutants on PvSUB1.

<p>Sequence and inhibitory activity of EETI-II mutants on PvSUB1.</p

Subtilisin catalytic site geometries.

<p>Subtilisin catalytic site geometries.</p

Structural alignment of the obtained PvSUB1 model (cyan) with the 3D-structure of Subtilisin E (gray, PDB 1SCJ) that was used as a template in the homology modelling.

<p>The catalytic triads in both proteins are highlighted with a stick representation. PvSUB1 catalytic triad: Asp 316, His 372 and Ser 549. Subtilisin E catalytic triad: Asp 32, His 64, Ser 221.</p