4JYB

MeaB, A Bacterial Homolog of MMAA, Bound to GMPPNP

4JYB の概要

• エントリーDOI: 10.2210/pdb4jyb/pdb
• 関連するPDBエントリー: 2QM7 2QM8 4JYC
• 分子名称: Methylmalonyl-CoA mutase accessory protein, PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER (3 entities in total)
• 機能のキーワード: alpha and beta protein, p-loop containing nucleoside triphosphate hydrolases, gtpase, metallochaperone, methylmalonyl-coa mutase (mcm), hydrolase
• 由来する生物種: Methylobacterium extorquens
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 72239.42

構造登録者

Koutmos, M.,Lofgren, M.,Padovani, D.,Banerjee, R. (登録日: 2013-03-29, 公開日: 2013-07-24, 最終更新日: 2023-09-20)

主引用文献

Lofgren, M.,Padovani, D.,Koutmos, M.,Banerjee, R.
A switch III motif relays signaling between a B12 enzyme and its G-protein chaperone.
Nat.Chem.Biol., 9:535-539, 2013

PubMed Abstract: Fidelity during cofactor assembly is essential for the proper functioning of metalloenzymes and is ensured by specific chaperones. MeaB, a G-protein chaperone for the coenzyme B12-dependent radical enzyme methylmalonyl-CoA mutase (MCM), uses the energy of GTP binding, hydrolysis or both to regulate cofactor loading into MCM, protect MCM from inactivation and rescue MCM that is inactivated during turnover. Typically, G proteins signal to client proteins using the conformationally mobile switch I and II loops. Crystallographic snapshots of MeaB reported herein reveal a new switch III element that has substantial conformational plasticity. Using alanine-scanning mutagenesis, we demonstrate that the switch III motif is critical for bidirectional signal transmission of the GTPase-activating protein activity of MCM and the chaperone functions of MeaB in the MeaB-MCM complex. Mutations in the switch III loop identified in patients corrupt this interprotein communication and lead to methylmalonic aciduria, an inborn error of metabolism.

PubMed: 23873214
DOI: 10.1038/nchembio.1298

実験手法

X-RAY DIFFRACTION (2.1 Å)