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Some representatives, however, preserve genes encoding tryptophan synthase, TrpAB \u2013 a bifunctional enzyme catalyzing the last two steps in <jats:sc>l\u2010<\/jats:sc>Trp synthesis. TrpA (subunit \u03b1) converts indole\u20103\u2010glycerol phosphate into indole and glyceraldehyde\u20103\u2010phosphate (\u03b1 reaction). The former compound is subsequently used by TrpB (subunit \u03b2) to produce <jats:sc>l\u2010<\/jats:sc>Trp in the presence of <jats:sc>l\u2010<\/jats:sc>Ser and a pyridoxal 5\u2032\u2010phosphate cofactor (\u03b2 reaction). Previous studies have indicated that in <jats:italic>Chlamydia<\/jats:italic>, TrpA has lost its catalytic activity yet remains associated with TrpB to support the \u03b2 reaction. Here, we provide detailed analysis of the TrpAB from <jats:italic>C. trachomatis<\/jats:italic> D\/UW\u20103\/CX, confirming that accumulation of mutations in the active site of TrpA renders it enzymatically inactive, despite the conservation of the catalytic residues. We also show that TrpA remains a functional component of the TrpAB complex, increasing the activity of TrpB by four\u2010fold. The side chain of non\u2010conserved \u03b2Arg267 functions as cation effector, potentially rendering the enzyme less susceptible to the solvent ion composition. The observed structural and functional changes detected herein were placed in a broader evolutionary and genomic context, allowing identification of these mutations in relation to their <jats:italic>trp<\/jats:italic> gene contexts in which they occur. Moreover, in agreement with the <jats:italic>in vitro<\/jats:italic> data, partial relaxation of purifying selection for TrpA, but not for TrpB, was detected, reinforcing a partial loss of TrpA functions during the course of evolution.<\/jats:p>","DOI":"10.1002\/pro.4143","type":"journal-article","created":{"date-parts":[[2021,6,9]],"date-time":"2021-06-09T18:30:18Z","timestamp":1623263418000},"page":"1904-1918","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Catalytically impaired <scp>TrpA<\/scp> subunit of tryptophan synthase from <i>Chlamydia trachomatis<\/i> is an allosteric regulator of <scp>TrpB<\/scp>"],"prefix":"10.1002","volume":"30","author":[{"given":"Karolina","family":"Michalska","sequence":"first","affiliation":[{"name":"Center for Structural Genomics of Infectious Diseases University of Chicago  Chicago Illinois USA"},{"name":"Structural Biology Center, X\u2010ray Science Division Argonne National Laboratory  Argonne Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Wellington","sequence":"additional","affiliation":[{"name":"Department of Genetics, Broad Institute of MIT and Harvard  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Maltseva","sequence":"additional","affiliation":[{"name":"Center for Structural Genomics of Infectious Diseases University of Chicago  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Jedrzejczak","sequence":"additional","affiliation":[{"name":"Center for Structural Genomics of Infectious Diseases University of Chicago  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelly","family":"Selem\u2010Mojica","sequence":"additional","affiliation":[{"name":"Evolution of Metabolic Diversity Laboratory Unidad de Gen\u00f3mica Avanzada (Langebio)  Cinvestav Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. 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Structural Genomics of Infectious Diseases University of Chicago  Chicago Illinois USA"},{"name":"Structural Biology Center, X\u2010ray Science Division Argonne National Laboratory  Argonne Illinois USA"},{"name":"Department of Biochemistry and Molecular Biology University of Chicago  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,6,16]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"WHO guidelines for the treatment of Chlamydia trachomatis 2016 World Health Organization 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