Sandbox Reserved 768: Difference between revisions
From Proteopedia
Jump to navigationJump to search
Arwa Omary (talk | contribs) No edit summary |
Arwa Omary (talk | contribs) No edit summary |
||
| Line 9: | Line 9: | ||
'''Phenylalanine Hydroxylase''' (also known as Phenylalanine-4-monooxygenase or simply PAH) is the enzyme that catalyzes the conversion of L-phenylalanine into L-tyrosine by hydroxylation (addition of an -OH group) of the aromatic side chain of phenyalanine. This reaction is the initial and rate-limiting step in the phenylalanine catabolism pathway. | '''Phenylalanine Hydroxylase''' (also known as Phenylalanine-4-monooxygenase or simply PAH) is the enzyme that catalyzes the conversion of L-phenylalanine into L-tyrosine by hydroxylation (addition of an -OH group) of the aromatic side chain of phenyalanine. This reaction is the initial and rate-limiting step in the phenylalanine catabolism pathway. | ||
<Structure load='2pah' size='500' frame='true' align='right' caption='Dimeric Unit of Phenylalanine Hydroxylase with the iron atom in the active sites in brown. ' scene=' | <Structure load='2pah' size='500' frame='true' align='right' caption='Dimeric Unit of Phenylalanine Hydroxylase with the iron atom in the active sites in brown. ' scene='Insert optional scene name here'/> The tyrosine product (a non-essential amino acid) can then serve as a precursor to the synthesis of important neurotransmitters.<ref name= "flydal"> Flydal, Marte, and Aurora Martinez. "Phenylalanine Hydroxylase: Function, Structure, and Regulation." International Union of Biochemistry and Molecular Biology Journal 65.4 (2013): 341-349. Web. </ref>. | ||
PAH uses tetrahydrobiopterin (BH4) as a cofactor and has a nonheme iron atom bound to its active site. PAH is classified as an oxidoreductase, specifically enzyme class EC 1.14 since its mechanism of action involves the oxidation/reduction of its substrate. <ref name= "pdb"> http://www.rcsb.org/pdb/explore/explore.do?structureId=1J8U </ref>. | PAH uses tetrahydrobiopterin (BH4) as a cofactor and has a nonheme iron atom bound to its active site. PAH is classified as an oxidoreductase, specifically enzyme class EC 1.14 since its mechanism of action involves the oxidation/reduction of its substrate. <ref name= "pdb"> http://www.rcsb.org/pdb/explore/explore.do?structureId=1J8U </ref>. | ||
| Line 24: | Line 24: | ||
== Phenylalanine Hydroxylase Mechanism of Action == | == Phenylalanine Hydroxylase Mechanism of Action == | ||
PAH, belonging to the oxidoreductase enzyme class, acts by oxidizing/reducing its substrate. Specifically, PAH acts on paired donors with pteridine being a donor and first incorporates one atom of molecular oxygen into the aromatic ring of phenylalanine. <ref name= "pdb"/>. Then, it reduces the second oxygen atom to water using the two electrons that are supplied by the BH4 cofactor. BH4 is also hydroxylated at each turnover to produce pterin-4a-carbinolamine (4a-OH-BH4), with consequent dissociation from the enzyme. 4a-OHBH4 is dehydrated and reduced back to BH4 by the action of the enzyme pterin carbinolamine dehydratase. <ref name= "flydal"/>. | PAH, belonging to the oxidoreductase enzyme class, acts by oxidizing/reducing its substrate. Specifically, PAH acts on paired donors with pteridine being a donor and first incorporates one atom of molecular oxygen into the aromatic ring of phenylalanine. <ref name= "pdb"/>. Then, it reduces the second oxygen atom to water using the two electrons that are supplied by the BH4 cofactor. BH4 is also hydroxylated at each turnover to produce pterin-4a-carbinolamine (4a-OH-BH4), with consequent dissociation from the enzyme. 4a-OHBH4 is dehydrated and reduced back to BH4 by the action of the enzyme pterin carbinolamine dehydratase. <ref name= "flydal"/>. | ||
| Line 37: | Line 38: | ||
== Phenylalanine Hydroxylase Structure == | == Phenylalanine Hydroxylase Structure == | ||
<Structure load='1j8u' size='500' frame='true' align='right' caption='Catalytic Domain of Human Phenylalanine Hydroxylase Fe(II) in Complex with Tetrahydrobiopterin' scene= | <Structure load='1j8u' size='500' frame='true' align='right' caption='Catalytic Domain of Human Phenylalanine Hydroxylase Fe(II) in Complex with Tetrahydrobiopterin' scene='Insert optional scene name here'/> | ||
Although the full-length structure of mammalian PAH has not yet been clearly known, a large part of it has been identified. <ref name= "flydal"/>. It was solved by means of crystallizing the protein (at pH=7) to perform X-ray diffraction using molecular replacement. The search model used was based on the crystal structure of tyrosine hydroxylase because of the similarity between the two enzymes. <ref name="fusetti"> Fusetti, Fabrizia, Heidi Erlandsen, Torgeir Flatmark, and Raymond Stevens. "Structure of Tetrameric Human Phenylalanine Hydroxylase and Its Implications for Phenylketonuria." The Journal of Biological Chemistry 273.27 (1998): 16962-16967. Web. </ref>. The R-factor recorded was 0.251 and the mean B (or temperature) value was 33.0. <ref name= "pdb"/>. | Although the full-length structure of mammalian PAH has not yet been clearly known, a large part of it has been identified. <ref name= "flydal"/>. It was solved by means of crystallizing the protein (at pH=7) to perform X-ray diffraction using molecular replacement. The search model used was based on the crystal structure of tyrosine hydroxylase because of the similarity between the two enzymes. <ref name="fusetti"> Fusetti, Fabrizia, Heidi Erlandsen, Torgeir Flatmark, and Raymond Stevens. "Structure of Tetrameric Human Phenylalanine Hydroxylase and Its Implications for Phenylketonuria." The Journal of Biological Chemistry 273.27 (1998): 16962-16967. Web. </ref>. The R-factor recorded was 0.251 and the mean B (or temperature) value was 33.0. <ref name= "pdb"/>. | ||
