User:James Bahng/sandbox 1
From Proteopedia
(Difference between revisions)
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1HYO is an EC 3.7.1.2 hydrolase involved in the final step of the Phe/Tyr catabolic pathway, and <scene name='58/581360/Ligand_bound/1'>binds to Fumarylacetoacetate</scene> producing [[http://ec.asm.org/content/6/3/514/F1.large.jpg Fumarate and Acetoacetate]]. | 1HYO is an EC 3.7.1.2 hydrolase involved in the final step of the Phe/Tyr catabolic pathway, and <scene name='58/581360/Ligand_bound/1'>binds to Fumarylacetoacetate</scene> producing [[http://ec.asm.org/content/6/3/514/F1.large.jpg Fumarate and Acetoacetate]]. | ||
| - | The mechanism is not well understood, but is hypothesized that His-133 activates a nucleophilic water, which attacks the δ carbon, leading to cleavage. The resultant tetrahedral alkoxy transition state | + | The mechanism is not well understood, but is hypothesized that His-133 activates a nucleophilic water, which attacks the δ carbon, leading to cleavage. The resultant tetrahedral alkoxy transition state is thought to be stabazlied by Arg-237, Gln-240, and Lys-253 residues. |
| - | == Disease == | + | == Disease and Treatment == |
Mutations in 1HYO are responsible for hereditary tyrosemia Type I, a serious metabolic disease resulting in chronic inflammation of the liver and neuronal damage. It is in the same metabolic pathway as Phenylketonuria (PKU) in infants, and is treated similarly with strict dietary control and pharmacological inhibition of Phenylalanine hydroxylase, the key first enzyme in the degradation pathway. | Mutations in 1HYO are responsible for hereditary tyrosemia Type I, a serious metabolic disease resulting in chronic inflammation of the liver and neuronal damage. It is in the same metabolic pathway as Phenylketonuria (PKU) in infants, and is treated similarly with strict dietary control and pharmacological inhibition of Phenylalanine hydroxylase, the key first enzyme in the degradation pathway. | ||
In very serious acute cases, double liver/kidney transplant may be considered as an option as well. | In very serious acute cases, double liver/kidney transplant may be considered as an option as well. | ||
== Relevance == | == Relevance == | ||
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== Structural highlights == | == Structural highlights == | ||
| - | FAH is a homodimer made up of two 46 kDa subunits. The subunits form a cavity complementary in shape and charge to fumarylacetoacetate. The binding is coordinated by Ca2+, Arg and two Tyr(INSERT IMAGE LINK). The active residues in are His-133, acting as a base to activate a water, and Arg-237, Gln-240 and Lys-253 (INSERT IMAGE LINK)acting to stabilize the tetrahedral alkoxy transition state. | + | FAH is a homodimer made up of two 46 kDa subunits.<ref name=”placeholder”> testst </ref> The subunits form a cavity <scene name='58/581360/Close_up_showing_metal_ions/2'>complementary in shape and charge to fumarylacetoacetate</scene>. The binding is coordinated by Ca2+, Arg and two Tyr(INSERT IMAGE LINK). The active residues in are His-133, acting as a base to activate a water, and Arg-237, Gln-240 and Lys-253 (INSERT IMAGE LINK)acting to stabilize the tetrahedral alkoxy transition state. |
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</StructureSection> | </StructureSection> | ||
== References == | == References == | ||
| - | + | Bateman, R.L., Bhanumoorthy, P., Witte, J.F., McClard, R.W., Grompe, M., Timm, D.E. (2001) Mechanistic Inferences from the Crystal Structure of Fumarylacetoacetate Hydrolase with a Bound | |
| + | Phosphorus-based Inhibitor. Journal of Biological Chemistry, 207(18) 15284-15291 | ||
Revision as of 04:40, 1 April 2014
Structure of Fumarylacetoacetate Hydrolase with Phosphorus-based Inhibitor
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References
Bateman, R.L., Bhanumoorthy, P., Witte, J.F., McClard, R.W., Grompe, M., Timm, D.E. (2001) Mechanistic Inferences from the Crystal Structure of Fumarylacetoacetate Hydrolase with a Bound Phosphorus-based Inhibitor. Journal of Biological Chemistry, 207(18) 15284-15291
