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@article{2262423, author = {Giladi, Moshe and BarandEl, Michal Lisnyansky and Vankova, Pavla and Ferofontov, Alisa and Melvin, Emelia and Alkaderi, Suha and Kavan, Daniel and Redko, Boris and Haimov, Elvira and Wiener, Reuven and Man, Petr and Haitin, Yoni}, article_location = {New York}, article_number = {20}, doi = {http://dx.doi.org/10.1126/sciadv.abn1171}, keywords = {Lipids; Mass spectrometry; Rubber products; Stereochemistry}, language = {eng}, issn = {2375-2548}, journal = {Science advances}, title = {Structural basis for long-chain isoprenoid synthesis by cis-prenyltransferases}, url = {https://www.science.org/doi/10.1126/sciadv.abn1171}, volume = {8}, year = {2022} }
TY - JOUR ID - 2262423 AU - Giladi, Moshe - Bar-El, Michal Lisnyansky - Vankova, Pavla - Ferofontov, Alisa - Melvin, Emelia - Alkaderi, Suha - Kavan, Daniel - Redko, Boris - Haimov, Elvira - Wiener, Reuven - Man, Petr - Haitin, Yoni PY - 2022 TI - Structural basis for long-chain isoprenoid synthesis by cis-prenyltransferases JF - Science advances VL - 8 IS - 20 SP - 1-14 EP - 1-14 PB - American Association for the Advancement of Science SN - 23752548 KW - Lipids KW - Mass spectrometry KW - Rubber products KW - Stereochemistry UR - https://www.science.org/doi/10.1126/sciadv.abn1171 N2 - 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. ER -
GILADI, Moshe, Michal Lisnyansky BAR-EL, Pavla VANKOVA, Alisa FEROFONTOV, Emelia MELVIN, Suha ALKADERI, Daniel KAVAN, Boris REDKO, Elvira HAIMOV, Reuven WIENER, Petr MAN and Yoni HAITIN. Structural basis for long-chain isoprenoid synthesis by cis-prenyltransferases. \textit{Science advances}. New York: American Association for the Advancement of Science, 2022, vol.~8, No~20, p.~1-14. ISSN~2375-2548. Available from: https://dx.doi.org/10.1126/sciadv.abn1171.
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