DOPA decarboxylase: Difference between revisions

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The inhibitor <scene name='~~Sandbox~~/~~Active_site3~~/1'>carbiDOPA</scene> binds to the enzyme by forming a hydrazone linkage with PLP through its hydrazine moiety. The catechol ring of carbiDOPA is deeply buried in the active site cleft and is stabilized by <scene name='DOPA_decarboxylase/Vanderwaals/1'>van der waals contact</scene> with Ile-101 and Phe-103. The 4' hydroxyl group of the catechol ring participates in hydrogen bonding with <scene name='DOPA_decarboxylase/Thr-82/1'>Thr-82</scene>, further stabilizing the inhibitor in the active site cleft. PLP is further involved in substrate binding by forming a hydrogen bond to the 3' of the catechol ring. <scene name='DOPA_decarboxylase/His192/1'>His-192</scene>, a highly conserved residue of PLP-dependent decarboxylases <ref name="ishii">PMID:8889823 </ref> hydrogen bonds to the carboxylate group of carbiDOPA.

The inhibitor <scene name='DOPA_decarboxylase/Carbidopa/1'>carbiDOPA</scene> binds to the enzyme by forming a hydrazone linkage with PLP through its hydrazine moiety. The catechol ring of carbiDOPA is deeply buried in the active site cleft and is stabilized by <scene name='DOPA_decarboxylase/Vanderwaals/1'>van der waals contact</scene> with Ile-101 and Phe-103. The 4' hydroxyl group of the catechol ring participates in hydrogen bonding with <scene name='DOPA_decarboxylase/Thr-82/1'>Thr-82</scene>, further stabilizing the inhibitor in the active site cleft. PLP is further involved in substrate binding by forming a hydrogen bond to the 3' of the catechol ring. <scene name='DOPA_decarboxylase/His192/1'>His-192</scene>, a highly conserved residue of PLP-dependent decarboxylases <ref name="ishii">PMID:8889823 </ref> hydrogen bonds to the carboxylate group of carbiDOPA.

===Flexible Loop===

In all three crystal structures of DOPA decarboxylase solved to date, residues 328-339 are invisible in the electron density map. This is because these amino acids form a short mobile loop that is believed to be important to the catalytic mechanism of the enzyme <ref name="ishii">PMID:10082378 </ref>. During catalysis, this loop is proposed to lose its flexibility and extend toward the active site, both occluding the active site from solvent during catalysis and possibly even taking part in the catalytic mechanism. The mobile loop is found in other PLP-depended enzymes, such as glutamate 1-semialdehyde aminotransferase. The idea that this flexible loop plays an important role in catalysis is supported by the fact that it contains several highly conserved residues, Tyr-332 and Lys-334. The conformational change that occurs is thought to be a result of loop residues directly interacting with the inhbitor.

DOPA decarboxylase: Difference between revisions

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 [[image:l-dopa.png|thumb|200px|'''L-DOPA''']][[image:carbiDOPA.png|thumb|200px|'''carbiDOPA''']] [[image:benserazide.png|thumb|200px|'''benserazide''']]
-The inhibitor <scene name='Sandbox/Active_site3/1'>carbiDOPA</scene> binds to the enzyme by forming a hydrazone linkage with PLP through its hydrazine moiety. The catechol ring of carbiDOPA is deeply buried in the active site cleft and is stabilized by <scene name='DOPA_decarboxylase/Vanderwaals/1'>van der waals contact</scene> with Ile-101 and Phe-103. The 4' hydroxyl group of the catechol ring participates in hydrogen bonding with <scene name='DOPA_decarboxylase/Thr-82/1'>Thr-82</scene>, further stabilizing the inhibitor in the active site cleft. PLP is further involved in substrate binding by forming a hydrogen bond to the 3' of the catechol ring. <scene name='DOPA_decarboxylase/His192/1'>His-192</scene>, a highly conserved residue of PLP-dependent decarboxylases <ref name="ishii">PMID:8889823 </ref>  hydrogen bonds to the carboxylate group of carbiDOPA.
+The inhibitor <scene name='DOPA_decarboxylase/Carbidopa/1'>carbiDOPA</scene> binds to the enzyme by forming a hydrazone linkage with PLP through its hydrazine moiety. The catechol ring of carbiDOPA is deeply buried in the active site cleft and is stabilized by <scene name='DOPA_decarboxylase/Vanderwaals/1'>van der waals contact</scene> with Ile-101 and Phe-103. The 4' hydroxyl group of the catechol ring participates in hydrogen bonding with <scene name='DOPA_decarboxylase/Thr-82/1'>Thr-82</scene>, further stabilizing the inhibitor in the active site cleft. PLP is further involved in substrate binding by forming a hydrogen bond to the 3' of the catechol ring. <scene name='DOPA_decarboxylase/His192/1'>His-192</scene>, a highly conserved residue of PLP-dependent decarboxylases <ref name="ishii">PMID:8889823 </ref>  hydrogen bonds to the carboxylate group of carbiDOPA.
 ===Flexible Loop===
 In all three crystal structures of DOPA decarboxylase solved to date, residues 328-339 are invisible in the electron density map. This is because these amino acids form a short mobile loop that is believed to be important to the catalytic mechanism of the enzyme <ref name="ishii">PMID:10082378 </ref>. During catalysis, this loop is proposed to lose its flexibility and extend toward the active site, both occluding the active site from solvent during catalysis and possibly even taking part in the catalytic mechanism. The mobile loop is found in other PLP-depended enzymes, such as glutamate 1-semialdehyde aminotransferase. The idea that this flexible loop plays an important role in catalysis is supported by the fact that it contains several highly conserved residues, Tyr-332 and Lys-334. The conformational change that occurs is thought to be a result of loop residues directly interacting with the inhbitor.