7cx0

Crystal structure of a tyrosine decarboxylase from Enterococcus faecalis in complex with the cofactor PLP and inhibitor carbidopa

Structural highlights

7cx0 is a 3 chain structure with sequence from Enterococcus faecalis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.66Å
Ligands:	142, PLP
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TYRDC_ENTFA Catalyzes the decarboxylation of L-tyrosine to produce tyramine (PubMed:30659181). Plays a role in acid resistance since tyramine production via tyrosine decarboxylation appears to provide a cytosolic pH maintenance mechanism that helps the bacterium cope with acid stress such as that encountered in gastrointestinal tract (GIT) environments. Therefore, may contribute to the colonization of the human GIT by E.faecalis (PubMed:25529314).^[1] ^[2] Also involved in drug metabolism, being able to catalyze decarboxylation of levodopa (L-dopa) to dopamine. In gut microbiota this enzyme is in fact exclusively responsible for the decarboxylation of levodopa, and thus reduces in situ levels of levodopa in the treatment of Parkinson's disease. It was shown that abundance of bacterial tyrosine decarboxylase in the proximal small intestine - the primary site of levodopa absorption - contributes to interindividual variation in drug efficacy and can explain the requirement for an increased dosage regimen of levodopa treatment in Parkinson's disease patients.^[3]

References

↑ Perez M, Calles-Enríquez M, Nes I, Martin MC, Fernandez M, Ladero V, Alvarez MA. Tyramine biosynthesis is transcriptionally induced at low pH and improves the fitness of Enterococcus faecalis in acidic environments. Appl Microbiol Biotechnol. 2015 Apr;99(8):3547-58. PMID:25529314 doi:10.1007/s00253-014-6301-7
↑ van Kessel SP, Frye AK, El-Gendy AO, Castejon M, Keshavarzian A, van Dijk G, El Aidy S. Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson's disease. Nat Commun. 2019 Jan 18;10(1):310. PMID:30659181 doi:10.1038/s41467-019-08294-y
↑ van Kessel SP, Frye AK, El-Gendy AO, Castejon M, Keshavarzian A, van Dijk G, El Aidy S. Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson's disease. Nat Commun. 2019 Jan 18;10(1):310. PMID:30659181 doi:10.1038/s41467-019-08294-y

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OCA

[1] Perez M, Calles-Enríquez M, Nes I, Martin MC, Fernandez M, Ladero V, Alvarez MA. Tyramine biosynthesis is transcriptionally induced at low pH and improves the fitness of Enterococcus faecalis in acidic environments. Appl Microbiol Biotechnol. 2015 Apr;99(8):3547-58. PMID:25529314 doi:10.1007/s00253-014-6301-7

[2] van Kessel SP, Frye AK, El-Gendy AO, Castejon M, Keshavarzian A, van Dijk G, El Aidy S. Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson's disease. Nat Commun. 2019 Jan 18;10(1):310. PMID:30659181 doi:10.1038/s41467-019-08294-y

[3] van Kessel SP, Frye AK, El-Gendy AO, Castejon M, Keshavarzian A, van Dijk G, El Aidy S. Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson's disease. Nat Commun. 2019 Jan 18;10(1):310. PMID:30659181 doi:10.1038/s41467-019-08294-y

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[2]

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7cx0

Crystal structure of a tyrosine decarboxylase from Enterococcus faecalis in complex with the cofactor PLP and inhibitor carbidopa

Structural highlights

Function

References

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