Sandbox Reserved 1734: Difference between revisions

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Primary Structure:

The primary structure of each monomer of phenylalanine hydroxylase contains 452 residues, weighing around ~~52kDa~~ (7 & 10).

The primary structure of each monomer of phenylalanine hydroxylase contains 452 residues, weighing around 52 kilodaltons (7 & 10).

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Tertiary Structure:

The tertiary structure of each monomer of ~~PAH~~ is organized from 2 alpha helices and 4 beta-strands into an alpha-beta sandwich motif (BaBBaB fold). The structural motif of an alpha-beta sandwich motif has the 4 antiparallel beta-strands flanked on one side by the 2 alpha-helices (3 & 5). The tertiary structure of a phenylalanine hydroxylase protein is built from an N-terminal regulatory domain (residues 1-117), a catalytic domain (residues 118-410), and a tetramerization domain (residues 411-452) (1 & 5). The catalytic domain includes the binding sites for iron, substrate and cofactor. The binding sites are at residues 285, 290, and 330. The archetypical (ACT) domain is in the N-terminal regulatory domain where proposed enzyme binding to an allosteric site (residues 3-11) (1).

The tertiary structure of each monomer of phenylalanine hydroxylase is organized from 2 alpha helices and 4 beta-strands into an alpha-beta sandwich motif (BaBBaB fold). The structural motif of an alpha-beta sandwich motif has the 4 antiparallel beta-strands flanked on one side by the 2 alpha-helices (3 & 5). The tertiary structure of a phenylalanine hydroxylase protein is built from an N-terminal regulatory domain (residues 1-117), a catalytic domain (residues 118-410), and a tetramerization domain (residues 411-452) (1 & 5). The catalytic domain includes the binding sites for iron, substrate and cofactor. The binding sites are at residues 285, 290, and 330. The archetypical (ACT) domain is in the N-terminal regulatory domain where proposed enzyme binding to an allosteric site (residues 3-11) (1).

Quaternary Structure:

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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 (1).

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 (1).

PAH is an iron (Fe2+) containing enzyme. The iron binds to 2 histidines at the active site (1 & 5). The cofactors of PAH include 6R-L-erythro-tetrahydrobiopterin (BH4) and oxygen (5). 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 (1).

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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@@ Line 4: / Line 4: @@
 Primary Structure:
-The primary structure of each monomer of phenylalanine hydroxylase contains 452 residues, weighing around 52kDa (7 & 10).
+The primary structure of each monomer of phenylalanine hydroxylase contains 452 residues, weighing around 52 kilodaltons (7 & 10).
 <Structure load='1phz' size='250' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' />
@@ Line 12: / Line 12: @@
 Tertiary Structure:
-The tertiary structure of each monomer of PAH is organized from 2 alpha helices and 4 beta-strands into an alpha-beta sandwich motif (BaBBaB fold). The structural motif of an alpha-beta sandwich motif has the 4 antiparallel beta-strands flanked on one side by the 2 alpha-helices (3 & 5). The tertiary structure of a phenylalanine hydroxylase protein is built from an N-terminal regulatory domain (residues 1-117), a catalytic domain (residues 118-410), and a tetramerization domain (residues 411-452) (1 & 5). The catalytic domain includes the binding sites for iron, substrate and cofactor. The binding sites are at residues 285, 290, and 330. The archetypical (ACT) domain is in the N-terminal regulatory domain where proposed enzyme binding to an allosteric site (residues 3-11) (1).
+The tertiary structure of each monomer of phenylalanine hydroxylase is organized from 2 alpha helices and 4 beta-strands into an alpha-beta sandwich motif (BaBBaB fold). The structural motif of an alpha-beta sandwich motif has the 4 antiparallel beta-strands flanked on one side by the 2 alpha-helices (3 & 5). The tertiary structure of a phenylalanine hydroxylase protein is built from an N-terminal regulatory domain (residues 1-117), a catalytic domain (residues 118-410), and a tetramerization domain (residues 411-452) (1 & 5). The catalytic domain includes the binding sites for iron, substrate and cofactor. The binding sites are at residues 285, 290, and 330. The archetypical (ACT) domain is in the N-terminal regulatory domain where proposed enzyme binding to an allosteric site (residues 3-11) (1).
 Quaternary Structure:
@@ Line 18: / Line 18: @@
 <Structure load='2PHM' size='250' frame='true' align='left' caption='Human Tetramer' scene='Insert optional scene name here' />
-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 (1).
+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 (1).
 PAH is an iron (Fe2+) containing enzyme. The iron binds to 2 histidines at the active site (1 & 5). The cofactors of PAH include 6R-L-erythro-tetrahydrobiopterin (BH4) and oxygen (5). 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 (1).
 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.