Počet záznamů: 1
Structural basis for long-chain isoprenoid synthesis by cis-prenyltransferases
- 1.0557998 - MBÚ 2023 RIV US eng J - Článek v odborném periodiku
Giladi, M. - Bar-El, M. - Vaňková, Pavla - Ferofontov, A. - Melvin, E. - Alkaderi, S. - Kavan, Daniel - Redko, B. - Haimov, E. - Wiener, R. - Man, Petr - Haitin, Y.
Structural basis for long-chain isoprenoid synthesis by cis-prenyltransferases.
Science Advances. Roč. 8, č. 20 (2022), č. článku eabn1171. ISSN 2375-2548. E-ISSN 2375-2548
Grant CEP: GA MŠMT(CZ) LM2018127; GA MŠMT(CZ) ED1.1.00/02.0109
GRANT EU: European Commission(XE) 731077 - EU_FT-ICR_MS
Institucionální podpora: RVO:61388971
Klíčová slova: undecaprenyl-pyrophosphate synthase * length determination mechanism * nogo-b receptor * protein glycosylation * exchange * inhibitor * insights * mutation * subunit * complex
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 13.6, rok: 2022
Způsob publikování: Open access
https://www.science.org/doi/10.1126/sciadv.abn1171
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.
Trvalý link: http://hdl.handle.net/11104/0331948
Počet záznamů: 1