7PAY

Structure of the human heterotetrameric cis-prenyltransferase complex in complex with magnesium and GGsPP

7PAY の概要

• エントリーDOI: 10.2210/pdb7pay/pdb
• 関連するPDBエントリー: 7PAX
• 分子名称: Dehydrodolichyl diphosphate synthase complex subunit DHDDS, Dehydrodolichyl diphosphate synthase complex subunit NUS1, SULFATE ION, ... (6 entities in total)
• 機能のキーワード: dhdds, ngbr, hcit, cis-prenyltransferase, dolichol, transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 64000.44

構造登録者

Giladi, M.,Lisnyansky Bar-El, M.,Haitin, Y. (登録日: 2021-07-30, 公開日: 2022-06-01, 最終更新日: 2024-01-31)

主引用文献

Giladi, M.,Lisnyansky Bar-El, M.,Vankova, P.,Ferofontov, A.,Melvin, E.,Alkaderi, S.,Kavan, D.,Redko, B.,Haimov, E.,Wiener, R.,Man, P.,Haitin, Y.
Structural basis for long-chain isoprenoid synthesis by cis -prenyltransferases.
Sci Adv, 8:eabn1171-eabn1171, 2022

PubMed Abstract: 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 -prenyltransferase complex (h-PT), residing at the endoplasmic reticulum membrane and playing a crucial role in protein glycosylation. Crystallographic investigation of h-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.

PubMed: 35584224
DOI: 10.1126/sciadv.abn1171

実験手法

X-RAY DIFFRACTION (2.4 Å)