Sandbox Reserved 770: Difference between revisions
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'''Histidine137''' | '''Histidine137''' | ||
Formation of carbanion intermediate is promoted by the positioning of the NH2 group of Asn270 to share a hydrogen bond with the enolate oxygen of MIO, increasing the electropositivity of MIO methylidene group, shown in Figure 9. Abstraction of the pro-''S'' hydrogen from C3 of substrate to form product ''trans''-cinnamic acid is catalyzed by His137 residue on helix one, which is connected to loop regions on both its C and N termini, allowing for its movement. His137 is located near the C terminus with its negative pole directed toward the active site, thus increasing basicity of His137 so it can act as a base. Development and further stabilization of the carbanion are provided by the phenyl group of the substrate, helix dipoles directing positive poles toward residues, improved MIO electron-withdrawing capability (enhanced by positive poles of three alpha helices), and electron withdrawal from substrates carboxy group by residues of positive pole N termini in alpha helices. MIO group assists in the breakage of C-N bond of substrate to proceed carbanion intermediate to product ''trans''-cinnamate. Once C-N bond is broken by PAL, cinnamate leaves the active site by Lys468 chaperone. | Formation of carbanion intermediate is promoted by the positioning of the NH2 group of Asn270 to share a hydrogen bond with the enolate oxygen of MIO, increasing the electropositivity of MIO methylidene group, shown in Figure 9. Abstraction of the pro-''S'' hydrogen from C3 of substrate to form product ''trans''-cinnamic acid is catalyzed by His137 residue on helix one, which is connected to loop regions on both its C and N termini, allowing for its movement. His137 is located near the C terminus with its negative pole directed toward the active site, thus increasing basicity of His137 so it can act as a base. Development and further stabilization of the carbanion are provided by the phenyl group of the substrate, helix dipoles directing positive poles toward residues, improved MIO electron-withdrawing capability (enhanced by positive poles of three alpha helices), and electron withdrawal from substrates carboxy group by residues of positive pole N termini in alpha helices. MIO group assists in the breakage of C-N bond of substrate to proceed carbanion intermediate to product ''trans''-cinnamate. Once C-N bond is broken by PAL, cinnamate leaves the active site by Lys468 chaperone. | ||
==Reaction Mechanism== | |||
[[Image:L-phenylalanine.jpeg|275px|Figure 10. Chemical Structure of L-Phenylalanine substrate]] | |||
[[Image:E1cb_mechanism.png|275px|Figure 11. Elimination Unimolecular conjugate Base Mechanism showing carbanion intermediate. X is ammonia in this non-oxidative deamination reaction caused by the lyase.]] | |||
[[Image:L-Phe_PAL_t-cinnamic_acid.png|275px|Figure 12. L-Phenylalanine substrate with k1 being the slow first step creating the stable carbanion, followed by a rapid product synsthesis in products CIN and Ammonia in Phenylalanine Ammonia Lyase enzyme.]] | |||
