Sandbox Reserved 1734: Difference between revisions

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The substrate of phenylalanine hydroxylase is the amino acid L-phenylalanine. Phenylalanine binds between the regulatory domain and the interacting catalytic domain, near the sequence binding motif. The activation of PAH by L-phenylalanine induces a large conformational change, but a slow global conformational change. Full activation of PAH involves the shift and dimerization of the regulatory domains.

PAH is an iron (~~Fe3~~+) containing enzyme. The iron binds to 2 histidines at the active site. The cofactors of PAH include 6R-L-erythro-tetrahydrobiopterin (BH4) and oxygen. BH4 is sandwiched between hydrophobic residues and forms several hydrogen bonds with the N-terminal autoregulatory tail. BH4 binding causes a limited conformational change (mostly constrained to the N-terminal tail). PAH lacking this tail is not regulated by either BH4 or L-phenylalanine and is constitutively active. The BH4 binding-site is flanked by the N-terminal (residues 21-32), the active-site lid (130-150), the Fe+2-coordinating residues, the Beta 6-alpha 7 loop (residues 245-251), and F254.

PAH is an iron (Fe2+) containing enzyme. The iron binds to 2 histidines at the active site. The cofactors of PAH include 6R-L-erythro-tetrahydrobiopterin (BH4) and oxygen. BH4 is sandwiched between hydrophobic residues and forms several hydrogen bonds with the N-terminal autoregulatory tail. BH4 binding causes a limited conformational change (mostly constrained to the N-terminal tail). PAH lacking this tail is not regulated by either BH4 or L-phenylalanine and is constitutively active. The BH4 binding-site is flanked by the N-terminal (residues 21-32), the active-site lid (130-150), the Fe+2-coordinating residues, the Beta 6-alpha 7 loop (residues 245-251), and F254.

Tetrahydrobiopterin induces a negative heterotropic allosteric effect on the enzyme, which is observed as the activation rate is slower for the BH4 holoprotein than compared to the unbound enzyme. Prior to BH4 binding, (PAH unbound state) a polar and salt-bridge interaction network links the three PAH domains.

Sandbox Reserved 1734: Difference between revisions

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 The substrate of phenylalanine hydroxylase is the amino acid L-phenylalanine. Phenylalanine binds between the regulatory domain and the interacting catalytic domain, near the sequence binding motif. The activation of PAH by L-phenylalanine induces a large conformational change, but a slow global conformational change. Full activation of PAH involves the shift and dimerization of the regulatory domains.
-PAH is an iron (Fe3+) containing enzyme. The iron binds to 2 histidines at the active site. The cofactors of PAH include 6R-L-erythro-tetrahydrobiopterin (BH4) and oxygen. BH4 is sandwiched between hydrophobic residues and forms several hydrogen bonds with the N-terminal autoregulatory tail. BH4 binding causes a limited conformational change (mostly constrained to the N-terminal tail). PAH lacking this tail is not regulated by either BH4 or L-phenylalanine and is constitutively active. The BH4 binding-site is flanked by the N-terminal (residues 21-32), the active-site lid (130-150), the Fe+2-coordinating residues, the Beta 6-alpha 7 loop (residues 245-251), and F254.
+PAH is an iron (Fe2+) containing enzyme. The iron binds to 2 histidines at the active site. The cofactors of PAH include 6R-L-erythro-tetrahydrobiopterin (BH4) and oxygen. BH4 is sandwiched between hydrophobic residues and forms several hydrogen bonds with the N-terminal autoregulatory tail. BH4 binding causes a limited conformational change (mostly constrained to the N-terminal tail). PAH lacking this tail is not regulated by either BH4 or L-phenylalanine and is constitutively active. The BH4 binding-site is flanked by the N-terminal (residues 21-32), the active-site lid (130-150), the Fe+2-coordinating residues, the Beta 6-alpha 7 loop (residues 245-251), and F254.
 Tetrahydrobiopterin induces a negative heterotropic allosteric effect on the enzyme, which is observed as the activation rate is slower for the BH4 holoprotein than compared to the unbound enzyme. Prior to BH4 binding, (PAH unbound state) a polar and salt-bridge interaction network links the three PAH domains.