MRYLH peptide bound in the active site of P450Blt. MRYLH is rendered in yellow sticks, with residues involved in hydrogen bonding─either directly or water-mediated, dispersed as sticks and labeled. Hydrogen bonds are depicted with dashed light magenta lines, highlighting the network of interactions between MRYLH and the active site residues. Red spheres represent water molecules that participate in this bonding network. The peptide substrate is aligned perpendicular to the I-helix, forming multiple hydrogen bonds; notably, the C-terminal carboxylate of MRYLH is coordinated between Arg-230 on the I-helix and Arg-188 on the G-helix. The N-terminal methionine of the substrate is situated close to Met-172 on the F-helix. Directly above haem pyrrole ring C, Tyr-3 of MRYLH establishes a critical hydrogen bond with Ser-239 on the I-helix. The backbone NH group of Tyr-3 is part of a hydrogen bond network with two water molecules, demonstrating intricate water-mediated interactions. His-5, positioned parallel to helix I, is hydrogen-bonded through its Ne2 to His-234. The presence of the substrate induces Gln-84 to assume an alternative rotameric state, allowing a hydrogen bond to the substrate, illustrated with a light magenta arrow to indicate this dynamic conformational shift.
