Sandbox Reserved 1734: Difference between revisions
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Alpha Helix: Pink, Beta Stand: Yellow |
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The primary structure of each monomer of phenylalanine hydroxylase contains 452 residues, weighing around 52 kilodaltons (1 & 2). | The primary structure of each monomer of phenylalanine hydroxylase contains 452 residues, weighing around 52 kilodaltons (1 & 2). | ||
<Structure load='1phz' size=' | <Structure load='1phz' size='350' frame='true' align='right' caption='Rat Tetramer Phosphorylated' scene='' /> | ||
Secondary Structure: | Secondary Structure: | ||
Phenylalanine hydroxylase (PAH) contains right-handed alpha helices and antiparallel beta-strands in its secondary structure (3 & 4). There are some amino acids that don't have any secondary structure, and these are found in the loop containing regions. The loop containing regions are residues Leucine 42-Valine 45, Aspartic acid 59-Histidine 69, Serine 70-Aspartic acid 75, and Histidine 82-Valine 90 (3). <scene name='91/919043/ | Phenylalanine hydroxylase (PAH) contains right-handed alpha helices and antiparallel beta-strands in its secondary structure (3 & 4). There are some amino acids that don't have any secondary structure, and these are found in the loop containing regions. The loop containing regions are residues Leucine 42-Valine 45, Aspartic acid 59-Histidine 69, Serine 70-Aspartic acid 75, and Histidine 82-Valine 90 (3). <scene name='91/919043/Secondary_structure/1'>Secondary Structure</scene> | ||
Tertiary Structure: | Tertiary Structure: | ||
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Quaternary Structure: | Quaternary Structure: | ||
The quaternary structure of PAH is a homotetramer, dimer of dimers. It is a multidomain, homo-oligomeric protein with dihedral (D2) symmetry (3 & 6). | The quaternary structure of PAH is a homotetramer, dimer of dimers. It is a multidomain, homo-oligomeric protein with dihedral (D2) symmetry (3 & 6). | ||
==Substrate & Catalysis== | ==Substrate & Catalysis== | ||
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 phenylalanine hydroxylase 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 (6). | 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 phenylalanine hydroxylase 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 (6). | ||
PAH is an iron (Fe2+) containing enzyme. The iron binds to 2 histidines at the active site (3 & 6). The cofactors of PAH include 6R-L-erythro-tetrahydrobiopterin (BH4) and oxygen (3). 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 | PAH is an iron (Fe2+) containing enzyme. The iron binds to 2 histidines at the active site (3 & 6). The cofactors of PAH include 6R-L-erythro-tetrahydrobiopterin (BH4) and oxygen (3). 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 (6). | ||
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. | 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. | ||
