Carbidopa: Difference between revisions

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== Molecular Mechanism ==

The ~~conversion of L-DOPA into dopamine is catalyzed by the~~ vitamin B6 (<scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>)-dependent enzyme DDC, an enzyme abundant in the nervous system as well as kidneys of humans<ref name="three">PMID: 7651438</ref> The catalytically active form of DDC is a homodimer, a feature typical of this class of enzymes<ref name= "four">PMID: 10673430</ref>. DDCs active site is located between the two monomers but is mainly composed of residues from only one of the monomers. The cofactor PLP binds to Lys 303 through a Schiff base linkage and a salt bridge between the carboxylate group of Asp 271 and the protonated pyridine nitrogen of PLP, which acts as a strong electron sink capable of stabilizing the carbanionic intermediates produced by active DDC. the cofactor is further stabilized in the enzyme through a network of hydrogen bonds. Carbidopa works by forming a hydrazone linkage with the PLP cofactor through its hydrazine moiety and blocking the DDC <scene name='74/746001/Active_site_dopa_final/1'>active site</scene> residues Ile 101' and Phe 103' in the substrate binding pocket with its catechol ring<ref name="five">doi:10.1038/nsb1101-963</ref>. In addition, the 4' hydroxyl group of Carbidopas catechol ring hydrogen bonds with THR 82 and the carboxylate group binds to HIS 192, a highly-conserved residue in PLP-dependent decarboxylases.<ref name="six">PMID: 8889823</ref> Due to the fact that Carbidopa cannot cross the blood-brain barrier, its inhibiting effects only are displayed in the periphery.

The vitamin B6 (<scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>)-dependent enzyme DDC, an enzyme abundant in the nervous system as well as kidneys of humans, catalyzes the conversion of L-DOPA into dopamine.<ref name="three">PMID: 7651438</ref> The catalytically active form of DDC is a homodimer, a feature typical of this class of enzymes.<ref name= "four">PMID: 10673430</ref> DDCs active site is located between the two monomers but is mainly composed of residues from only one of the monomers. The cofactor PLP binds to Lys 303 through a Schiff base linkage and a salt bridge between the carboxylate group of Asp 271 and the protonated pyridine nitrogen of PLP, which acts as a strong electron sink capable of stabilizing the carbanionic intermediates produced by active DDC. the cofactor is further stabilized in the enzyme through a network of hydrogen bonds. Carbidopa works by forming a hydrazone linkage with the PLP cofactor through its hydrazine moiety and blocking the DDC <scene name='74/746001/Active_site_dopa_final/1'>active site</scene> residues Ile 101' and Phe 103' in the substrate binding pocket with its catechol ring.<ref name="five">doi:10.1038/nsb1101-963</ref> In addition, the 4' hydroxyl group of Carbidopas catechol ring hydrogen bonds with THR 82 and the carboxylate group binds to HIS 192, a highly-conserved residue in PLP-dependent decarboxylases.<ref name="six">PMID: 8889823</ref> Due to the fact that Carbidopa cannot cross the blood-brain barrier, its inhibiting effects only are displayed in the periphery.

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Carbidopa: Difference between revisions

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 == Molecular Mechanism ==
-The conversion of L-DOPA into dopamine is catalyzed by the vitamin B6 (<scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>)-dependent enzyme DDC, an enzyme abundant in the nervous system as well as kidneys of humans<ref name="three">PMID: 7651438</ref> The catalytically active form of DDC is a homodimer, a feature typical of this class of enzymes<ref name= "four">PMID: 10673430</ref>. DDCs active site is located between the two monomers but is mainly composed of residues from only one of the monomers. The cofactor PLP binds to Lys 303 through a Schiff base linkage and a salt bridge between the carboxylate group of Asp 271 and the protonated pyridine nitrogen of PLP, which acts as a strong electron sink capable of stabilizing the carbanionic intermediates produced by active DDC. the cofactor is further stabilized in the enzyme through a network of hydrogen bonds. Carbidopa works by forming a hydrazone linkage with the PLP cofactor through its hydrazine moiety and blocking the DDC <scene name='74/746001/Active_site_dopa_final/1'>active site</scene> residues Ile 101' and Phe 103' in the substrate binding pocket with its catechol ring<ref name="five">doi:10.1038/nsb1101-963</ref>. In addition, the 4' hydroxyl group of Carbidopas catechol ring hydrogen bonds with THR 82 and the carboxylate group binds to HIS 192, a highly-conserved residue in PLP-dependent decarboxylases.<ref name="six">PMID: 8889823</ref> Due to the fact that Carbidopa cannot cross the blood-brain barrier, its inhibiting effects only are displayed in the periphery.
+The vitamin B6 (<scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>)-dependent enzyme DDC, an enzyme abundant in the nervous system as well as kidneys of humans, catalyzes the conversion of L-DOPA into dopamine.<ref name="three">PMID: 7651438</ref> The catalytically active form of DDC is a homodimer, a feature typical of this class of enzymes.<ref name= "four">PMID: 10673430</ref> DDCs active site is located between the two monomers but is mainly composed of residues from only one of the monomers. The cofactor PLP binds to Lys 303 through a Schiff base linkage and a salt bridge between the carboxylate group of Asp 271 and the protonated pyridine nitrogen of PLP, which acts as a strong electron sink capable of stabilizing the carbanionic intermediates produced by active DDC. the cofactor is further stabilized in the enzyme through a network of hydrogen bonds. Carbidopa works by forming a hydrazone linkage with the PLP cofactor through its hydrazine moiety and blocking the DDC <scene name='74/746001/Active_site_dopa_final/1'>active site</scene> residues Ile 101' and Phe 103' in the substrate binding pocket with its catechol ring.<ref name="five">doi:10.1038/nsb1101-963</ref> In addition, the 4' hydroxyl group of Carbidopas catechol ring hydrogen bonds with THR 82 and the carboxylate group binds to HIS 192, a highly-conserved residue in PLP-dependent decarboxylases.<ref name="six">PMID: 8889823</ref> Due to the fact that Carbidopa cannot cross the blood-brain barrier, its inhibiting effects only are displayed in the periphery.
 ==Interactions==