Structural basis for long-chain isoprenoid synthesis by
cis-prenyltransferases

J 2022

Structural basis for long-chain isoprenoid synthesis by cis-prenyltransferases

GILADI, Moshe, Michal Lisnyansky BAR-EL, Pavla VANKOVA, Alisa FEROFONTOV, Emelia MELVIN et. al.

Basic information

Original name

Structural basis for long-chain isoprenoid synthesis by cis-prenyltransferases

Authors

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

Edition

Science advances, New York, American Association for the Advancement of Science, 2022, 2375-2548

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10400 1.4 Chemical sciences

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 13.600

RIV identification code

RIV/00216224:14740/22:00128766

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1126/sciadv.abn1171

UT WoS

000798164800022

Keywords in English

Lipids; Mass spectrometry; Rubber products; Stereochemistry

Abstract

V originále

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.

Links

90127, large research infrastructures

Name: CIISB II

Citovat

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. 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.

@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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