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. 2023 Feb;597(4):557-572.
doi: 10.1002/1873-3468.14573. Epub 2023 Jan 20.

The Chlamydia trachomatis p-aminobenzoate synthase CADD is a manganese-dependent oxygenase that uses its own amino acid residues as substrates

Rowan Wooldridge  1 , Spenser Stone  1 , Andrew Pedraza  1 , W Keith Ray  1 , Richard F Helm  1 , Kylie D Allen  1
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Free article

The Chlamydia trachomatis p-aminobenzoate synthase CADD is a manganese-dependent oxygenase that uses its own amino acid residues as substrates

Rowan Wooldridge et al. FEBS Lett. 2023 Feb.
Free article

Abstract

CADD (chlamydia protein associating with death domains) is a p-aminobenzoate (pAB) synthase involved in a noncanonical route for tetrahydrofolate biosynthesis in Chlamydia trachomatis. Although previously implicated to employ a diiron cofactor, here, we show that pAB synthesis by CADD requires manganese and the physiological cofactor is most likely a heterodinuclear Mn/Fe cluster. Isotope-labeling experiments revealed that the two oxygen atoms in the carboxylic acid portion of pAB are derived from molecular oxygen. Further, mass spectrometry-based proteomic analyses of CADD-derived peptides demonstrated a glycine substitution at Tyr27, providing strong evidence that this residue is sacrificed for pAB synthesis. Additionally, Lys152 was deaminated and oxidized to aminoadipic acid, supporting its proposed role as a sacrificial amino group donor.

Keywords: Chlamydia; CADD; folate biosynthesis; metalloenzyme; oxygenase; self-sacrificing enzyme.

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