4JYC

MeaB, A Bacterial Homolog of MMAA, in its Apo form

Summary for 4JYC

• Entry DOI: 10.2210/pdb4jyc/pdb
• Related: 2QM7 2QM8 4JYB
• Descriptor: Methylmalonyl-CoA mutase accessory protein, GUANOSINE-5'-DIPHOSPHATE (3 entities in total)
• Functional Keywords: alpha and beta protein, p-loop containing nucleoside triphosphate hydrolases, gtpase, metallochaperone, methylmalonyl-coa mutase (mcm), chaperone
• Biological source: Methylobacterium extorquens
• Total number of polymer chains: 4
• Total formula weight: 142833.25

Authors

Koutmos, M.,Lofgren, M.,Padovani, D.,Banerjee, R. (deposition date: 2013-03-29, release date: 2013-07-24, Last modification date: 2023-09-20)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.2 Å)