User:James Bahng/sandbox 1
From Proteopedia
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== Structure of Fumarylacetoacetate Hydrolase with Phosphorus-based Inhibitor == | == Structure of Fumarylacetoacetate Hydrolase with Phosphorus-based Inhibitor == | ||
| - | <StructureSection load='1hyo' size='340' side='right' caption=' | + | <StructureSection load='1hyo' size='340' side='right' caption='Fumarylacetoacetate Hydrolase' scene=''> |
| - | 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 [http://www.ebi.ac.uk/intenz/query?cmd=SearchEC&ec=3.7.1 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 is thought to be stabazlied by Arg-237, Gln-240, and Lys-253 residues. | + | 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. As with all of the EC 3.7.1 class enzymes, the key to the C-C cleavage is the metal ion that lines up with the carbon to be cleaved. |
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FAH is a homodimer made up of two 46 kDa subunits.<ref name=”placeholder”> 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 | FAH is a homodimer made up of two 46 kDa subunits.<ref name=”placeholder”> 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 | Phosphorus-based Inhibitor. Journal of Biological Chemistry, 207(18) 15284-15291 | ||
| - | </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 | + | </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. The active residues in are His-133, acting as a base to activate a water, and Arg-237, Gln-240 and Lys-253 acting to stabilize the tetrahedral alkoxy transition state. |
Revision as of 04:56, 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
