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Structural basis for long-chain isoprenoid synthesis by cis-prenyltransferases
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SYSNO ASEP 0557998 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Structural basis for long-chain isoprenoid synthesis by cis-prenyltransferases Tvůrce(i) Giladi, M. (IL)
Bar-El, M. (IL)
Vaňková, Pavla (MBU-M) ORCID
Ferofontov, A. (IL)
Melvin, E. (IL)
Alkaderi, S. (IL)
Kavan, Daniel (MBU-M) RID, ORCID
Redko, B. (IL)
Haimov, E. (IL)
Wiener, R. (IL)
Man, Petr (MBU-M) RID, ORCID
Haitin, Y. (IL)Číslo článku eabn1171 Zdroj.dok. Science Advances. - : American Association for the Advancement of Science - ISSN 2375-2548
Roč. 8, č. 20 (2022)Poč.str. 14 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova undecaprenyl-pyrophosphate synthase ; length determination mechanism ; nogo-b receptor ; protein glycosylation ; exchange ; inhibitor ; insights ; mutation ; subunit ; complex Vědní obor RIV CE - Biochemie Obor OECD Biochemistry and molecular biology CEP LM2018127 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy ED1.1.00/02.0109 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Způsob publikování Open access Institucionální podpora MBU-M - RVO:61388971 UT WOS 000798164800022 EID SCOPUS 85130283475 DOI 10.1126/sciadv.abn1171 Anotace Isoprenoids are synthesized by the prenyltransferase superfamily, which is subdivided according to the product stereoisomerism and length. In short- and medium-chain isoprenoids, product length correlates with active site volume. However, enzymes synthesizing long-chain products and rubber synthases fail to conform to this paradigm, because of an unexpectedly small active site. Here, we focused on the human cis-prenyltransferase complex (hcis-PT), residing at the endoplasmic reticulum membrane and playing a crucial role in protein glycosylation. Crystallographic investigation of hcis-PT along the reaction cycle revealed an outlet for the elongating product. Hydrogen-deuterium exchange mass spectrometry analysis showed that the hydrophobic active site core is flanked by dynamic regions consistent with separate inlet and outlet orifices. Last, using a fluorescence substrate analog, we show that product elongation and membrane association are closely correlated. Together, our results support direct membrane insertion of the elongating isoprenoid during catalysis, uncoupling active site volume from product length. Pracoviště Mikrobiologický ústav Kontakt Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Rok sběru 2023 Elektronická adresa https://www.science.org/doi/10.1126/sciadv.abn1171
Počet záznamů: 1