{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:56:20Z","timestamp":1792454180420,"version":"4.5.0"},"reference-count":41,"publisher":"National Academy of Sciences","issue":"13","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,4]]},"abstract":"<jats:p>\n                    The yeast ABC transporter Pdr5 plays a major role in drug resistance against a large number of structurally unrelated compounds. Although Pdr5 has been extensively studied, many important aspects regarding its molecular mechanisms remain unresolved. For example, a striking degeneration of conserved amino acid residues exists in the nucleotide binding domains (NBDs), but their functional relevance is unknown. Here, we performed\n                    <jats:italic>in vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vitro<\/jats:italic>\n                    experiments to address the functional asymmetry of NBDs. It became evident by ATPase activity and drug transport studies that catalysis at only one of the two NBD composite sites is crucial for protein function. Furthermore, mutations of the proposed \u201ccatalytic carboxylate\u201d (E1036) and the \u201ccatalytic dyad histidine\u201d (H1068) were characterized. Although a mutation of the glutamate abolished ATPase activity and substrate transport, mutation of H1068 had no influence on ATP consumption. However, the H1068A mutation abolished rhodamine transport\n                    <jats:italic>in vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vitro<\/jats:italic>\n                    , while leaving the transport of other substrates unaffected. By contrast to mammalian P-glycoprotein (P-gp), the ATPase activity of yeast Pdr5 is not stimulated by the addition of substrates, indicating that Pdr5 is an uncoupled ABC transporter that constantly hydrolyses ATP to ensure active substrate transport. Taken together, our data provide important insights into the molecular mechanism of Pdr5 and suggest that not solely the transmembrane domains dictate substrate selection.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0800191105","type":"journal-article","created":{"date-parts":[[2008,3,20]],"date-time":"2008-03-20T21:27:35Z","timestamp":1206048455000},"page":"5069-5074","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":138,"title":["A mutation of the H-loop selectively affects rhodamine transport by the yeast multidrug ABC transporter Pdr5"],"prefix":"10.1073","volume":"105","author":[{"given":"Robert","family":"Ernst","sequence":"first","affiliation":[{"name":"*Institute of Biochemistry, Heinrich Heine University Duesseldorf, Universitaetsstrasse 1, 40225 Duesseldorf, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Kueppers","sequence":"additional","affiliation":[{"name":"*Institute of Biochemistry, Heinrich Heine University Duesseldorf, Universitaetsstrasse 1, 40225 Duesseldorf, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia M.","family":"Klein","sequence":"additional","affiliation":[{"name":"Max F. Perutz Laboratories, Medical University Vienna, Campus Vienna Biocenter, Dr. Bohr-Gasse 9\/2, A-1030 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Schwarzmueller","sequence":"additional","affiliation":[{"name":"Max F. Perutz Laboratories, Medical University Vienna, Campus Vienna Biocenter, Dr. Bohr-Gasse 9\/2, A-1030 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Kuchler","sequence":"additional","affiliation":[{"name":"Max F. 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