The OMIM entry 612349 is for PHENYLALANINE HYDROXYLASE; PAH.
Phenylalanine hydroxylase is an enzyme that catalyzes the
hydroxylation of phenylalanine to tyrosine, the rate-limiting step in
phenylalanine catabolism. The reaction is dependent on tetrahydrobiopterin
(BH4), as a cofactor, molecular oxygen, and iron. Phenylketonuria (PKU) is an
autosomal recessive inborn error of metabolism resulting from a deficiency of
PAH.
The cytogenetic location of the PAH gene: 12q23.2 . It is located on the 12 chromosome on the longer arm “q” at
the position 23.2 from the centromere.
Gene Structure: The PAH gene spans 90 kb and contains 13
exons.
The first two Allelic variants of the gene PAH are 0.0001 and 0.0002.
0.0001PHENYLKETONURIA: PAH, IVS12DS, G-A, +1 :The first PKU mutation identified in the PAH gene was a
single base change (GT-to-AT) in the canonical 5-prime splice donor site of
intron 12. The splicing mutation was the most prevalent PKU allele among
Caucasians. The GT-to-AT substitution at
the 5-prime splice donor site of intron 12 resulted in the skipping of the
preceding exon during RNA splicing. cDNA clones had shown an internal
116-basepair deletion corresponding precisely to exon 12 and leading to the
synthesis of the truncated protein lacking the C-terminal 52 amino acids.
Thus I picked the second allele will be discussing its characteristics.
0002PHENYLKETONURIA: PAH, ARG408TRP; This defect is caused by a CGG-to-TGG transition in exon 12,
resulting in an amino acid substitution (arg-to-trp) at residue 408 (R408W) of
PAH. This point mutation another example of CpG mutation is in linkage disequilibrium with RFLP
haplotype-2 alleles that make up about 20% of mutant PAH genes.
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| The trinucleotide CGG at position 122-124-code for Arginine |
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| The Amino-Acid at the positon 408 is Arginine |
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| The trinucleotide TGG at position 122-124-code for Tryptophan |
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| The Amino-Acid at the positon 408 is Tryptophas |
The PDB ID of the structure I am using is 2PAH. It is tetrameric Human Phenylalanine Hydroxylase.
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| PDB ID: 2PAH |
The image of the PAH gene with the site (408Arginine) highlighted.
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| The Arginine at positon 408 is highlighed in the spacefill view |
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| The conttext region around the AA Arginine 408 |
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| Arginine at position 408 in the Tube view in Cn3D |
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| Arginine at position 408 and the context area the Tube view in Cn3D |
The secondary structure in the PDB predict the Amino Acid 408 Arginine to be an area where no region is assigned as per the DSSP algorithm.
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| The secondary structure in the PDB with Arginine in black region region. |
The prediction by the algorithms in protean DNASTAR is as follows.
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| The secondary structure prediction by the algorithm in protean |
According to the Garnier Robinson the Arginine at position 408 is assigned to Beta region.
The Chou-Fasman algorithm assigned the Arginine at position 408 to Turn region.
The Tube view in the Cn3D also shows the Arginine in the trun region of the tertiary structure.
The prediction by the algorithms in Protean 3Dis as follows.
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| Secondary-structure by Chou Fasman Algorithm in Protean 3D the Arginine 408 in Beta region |
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| Secondary-structure by Deleage-Roux Algorithm in Protean 3D the Arginine 408 in Beta region |
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| Secondary-structure by Garnier Robson Algorithm in Protean 3D the Arginine 408 in coil region |
Secondary-structure by Chou Fasman Algorithm in Protean 3D the Arginine 408 in Beta region.
Secondary-structure by Deleage-Roux Algorithm in Protean 3D the Arginine 408 in Beta region.
Secondary-structure by Garnier Robson Algorithm in Protean 3D the Arginine 408 in coil region.
The Tube style of the Cn3D also show Arginine in the coil region. The DSSP algorithm in PDB does not assign any secondary structure to the position 408 for Arginine.
Chou-Fasman assume that each amino acid individually influence the secondary structure of protein, while the Garnier-Robson take into account the influence on the secondary structure
of the amino acids flanking the central amino acid residues. The prediction reliability of these algorithms is 50% to 60%.
The secondary structure prediction is the begining point in the prediction of the three-dimensional structure of the protein. There is a correlation betweem the amino acid sequence and
secondary structure. The short stretch of amino acid will adopt one kind of secondary structure or another.If one amino acid is taken as central the neighboring amino acids ranging from
5-40 residues long for helices and 5-10 residues long for b-sheets. The earlier algorithms could not detect the influence of distant amino acids with each other while the recent
algorithms also account for the possibility of more distanct interactions thus increasing the prediction rate to 75%.
The tertiary structure of my gene PAH in the structure part of Protean3D.
Secondary-structure by Deleage-Roux Algorithm in Protean 3D the Arginine 408 in Beta region.
Secondary-structure by Garnier Robson Algorithm in Protean 3D the Arginine 408 in coil region.
The Tube style of the Cn3D also show Arginine in the coil region. The DSSP algorithm in PDB does not assign any secondary structure to the position 408 for Arginine.
Chou-Fasman assume that each amino acid individually influence the secondary structure of protein, while the Garnier-Robson take into account the influence on the secondary structure
of the amino acids flanking the central amino acid residues. The prediction reliability of these algorithms is 50% to 60%.
The secondary structure prediction is the begining point in the prediction of the three-dimensional structure of the protein. There is a correlation betweem the amino acid sequence and
secondary structure. The short stretch of amino acid will adopt one kind of secondary structure or another.If one amino acid is taken as central the neighboring amino acids ranging from
5-40 residues long for helices and 5-10 residues long for b-sheets. The earlier algorithms could not detect the influence of distant amino acids with each other while the recent
algorithms also account for the possibility of more distanct interactions thus increasing the prediction rate to 75%.
The tertiary structure of my gene PAH in the structure part of Protean3D.
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| The Arginine at 408 position is seen in the coil region of the secondary structure in Protean 3D |
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