Literature summary for 1.14.11.2 extracted from

Timmins, A.; Saint-Andre, M.; de Visser, S.P.
Understanding how prolyl-4-hydroxylase structure steers a ferryl oxidant toward scission of a strong C-H bond (2017), J. Am. Chem. Soc., 139, 9855-9866 .

Search for more literature for 1.14.11.2

Protein Variants

Protein Variants	Comment	Organism
additional information	wild-type and mutant enzymes structure-function analysis by quantum mechanics/molecular mechanics (QM/MM) and molecular dynamics (MD) study, QM/MM optimized hydrogen atom abstraction structures for wild-type and mutants at the C4 positions of the substrate, overview	Homo sapiens
W243F	site-directed mutagenesis, mutant structure analysis compared to the wild-type enzyme, the substrate reaches equilibrium within 10 ns. Replacement of Trp243 by Phe increases the accessibility to the oxidant	Homo sapiens
W243G	site-directed mutagenesis, mutant structure analysis compared to the wild-type enzyme, the substrate equilibrium is not reached after 10 ns	Homo sapiens
Y140F	site-directed mutagenesis, mutant structure analysis compared to the wild-type enzyme, the substrate reaches equilibrium within 10 ns, inactive mutant	Homo sapiens
Y140G	site-directed mutagenesis, mutant structure analysis compared to the wild-type enzyme, the substrate reaches equilibrium within 10 ns	Homo sapiens
Y140G/W243G	site-directed mutagenesis, mutant structure analysis compared to the wild-type enzyme, the substrate equilibrium is not reached after 10 ns. The Y140G/W243G double mutant shows the accumulative effect of both the Y140G and W243G mutations	Homo sapiens

KM Value [mM]

KM Value [mM]	KM Value Maximum [mM]	Substrate	Comment	Organism	Structure
additional information	-	additional information	kinetic analysis	Homo sapiens

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Fe2+	a non-heme iron hydroxylase	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
additional information	Homo sapiens	prolyl-4-hydroxylase (P4H) is a non-heme iron hydroxylase that regio- and stereospecifically hydroxylates proline residues in a peptide chain into R-4-hydroxyproline. In P4H, a strong aliphatic C-H bond is activated, while thermodynamically much weaker aliphatic C-H groups, that is, at the C3 and C5 positions, are untouched	?	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P13674	-	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
additional information	prolyl-4-hydroxylase (P4H) is a non-heme iron hydroxylase that regio- and stereospecifically hydroxylates proline residues in a peptide chain into R-4-hydroxyproline. In P4H, a strong aliphatic C-H bond is activated, while thermodynamically much weaker aliphatic C-H groups, that is, at the C3 and C5 positions, are untouched	Homo sapiens	?	-	?

Synonyms

Synonyms	Comment	Organism
P4H	-	Homo sapiens
prolyl-4-hydroxylase	-	Homo sapiens

General Information

General Information	Comment	Organism
malfunction	mutations, where the hydrogen bonding network that involves the Tyr140 and Trp243 residues is disrupted, lead to major changes in folding of the protein and the size and shape of the substrate binding pocket. Trp243 mutation has major long-range effects	Homo sapiens
additional information	the active site of the protein contains two aromatic residues (Tyr140 and Trp243). Trp243 is involved in key protein loop-loop interactions that affect the shape and size of the substrate binding pocket. By contrast, the Tyr140 residue is shown to guide the regio- and stereoselectivity by holding the substrate and ferryl oxidant in a specific orientation through hydrogen bonding and Pi-stacking interactions. The Tyr140 residue is involved in expelling the product from the binding pocket after the reaction is completed. Wild-type and mutant enzymes structure-function analysis by quantum mechanics/molecular mechanics (QM/MM) and molecular dynamics (MD) study, QM/MM optimized hydrogen atom abstraction structures for wild-type and mutants at the C4 positions of the substrate, overview	Homo sapiens
physiological function	prolyl-4-hydroxylase (P4H) is a non-heme iron hydroxylase that regio- and stereospecifically hydroxylates proline residues in a peptide chain into R-4-hydroxyproline, which is essential for collagen cross-linking purposes in the human body	Homo sapiens

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Release 2023.1 (January 2023)