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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,6,28]]},"abstract":"<jats:p>\n                    Construction and remodeling of the bacterial peptidoglycan (PG) cell wall must be carefully coordinated with cell growth and division. Central to cell wall construction are hydrolases that cleave bonds in peptidoglycan. These enzymes also represent potential new antibiotic targets. One such hydrolase, the amidase LytH in\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    , acts to remove stem peptides from PG, controlling where substrates are available for insertion of new PG strands and consequently regulating cell size. When it is absent, cells grow excessively large and have division defects. For activity, LytH requires a protein partner, ActH, that consists of an intracellular domain, a large rhomboid protease domain, and three extracellular tetratricopeptide repeats (TPRs). Here, we demonstrate that the amidase-activating function of ActH is entirely contained in its extracellular TPRs. We show that ActH binding stabilizes metals in the LytH active site and that LytH metal binding in turn is needed for stable complexation with ActH. We further present a structure of a complex of the extracellular domains of LytH and ActH. Our findings suggest that metal cofactor stabilization is a general strategy used by amidase activators and that ActH houses multiple functions within a single protein.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2201141119","type":"journal-article","created":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T00:00:48Z","timestamp":1655942448000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":12,"title":["Metal cofactor stabilization by a partner protein is a widespread strategy employed for amidase activation"],"prefix":"10.1073","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9884-2382","authenticated-orcid":false,"given":"Julia E.","family":"Page","sequence":"first","affiliation":[{"name":"Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4615-6775","authenticated-orcid":false,"given":"Meredith A.","family":"Skiba","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7212-0296","authenticated-orcid":false,"given":"Truc","family":"Do","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1467-1222","authenticated-orcid":false,"given":"Andrew C.","family":"Kruse","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0545-914X","authenticated-orcid":false,"given":"Suzanne","family":"Walker","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2022,6,22]]},"reference":[{"key":"e_1_3_4_1_2","first-page":"1","article-title":"Envelope structures of gram-positive bacteria","volume":"404","author":"Rajagopal M.","year":"2017","unstructured":"M. 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E. Page M. A. Skiba T. Do A. C. Kruse S. Walker 7TJ4. Protein Data Bank. https:\/\/www.rcsb.org\/structure\/unreleased\/7TJ4. 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