9CG2

DUF512 protein from Pyrococcus furiosus

Summary for 9CG2

• Entry DOI: 10.2210/pdb9cg2/pdb
• Descriptor: Elp3/MiaA/NifB-like radical SAM core domain-containing protein, POTASSIUM ION, COBALAMIN, ... (7 entities in total)
• Functional Keywords: radical s-adenosylmethionine enzyme, duf512, oxidoreductase
• Biological source: Pyrococcus furiosus
• Total number of polymer chains: 1
• Total formula weight: 43643.56

Authors

Wang, B.,Radle, M.I.,Peduzzi, O.,Solinski, A.,Knox, H.L.,Cui, J.,Maurya, R.,Yennawar, N.,Booker, S.J. (deposition date: 2024-06-28, release date: 2025-03-05, Last modification date: 2025-09-17)

Primary citation

Wang, B.,Solinski, A.E.,Radle, M.I.,Peduzzi, O.M.,Knox, H.L.,Cui, J.,Maurya, R.K.,Yennawar, N.H.,Booker, S.J.
Structural Evidence for DUF512 as a Radical S -Adenosylmethionine Cobalamin-Binding Domain.
Acs Bio Med Chem Au, 4:319-330, 2024

PubMed Abstract: Cobalamin (Cbl)-dependent radical -adenosylmethionine (SAM) enzymes constitute a large subclass of radical SAM (RS) enzymes that use Cbl to catalyze various types of reactions, the most common of which are methylations. Most Cbl-dependent RS enzymes contain an N-terminal Rossmann fold that aids Cbl binding. Recently, it has been demonstrated that the methanogenesis marker protein 10 (Mmp10) requires Cbl to methylate an arginine residue in the α-subunit of methyl coenzyme M reductase. However, Mmp10 contains a Cbl-binding domain in the C-terminal region of its primary structure that does not share significant sequence similarity with canonical RS Cbl-binding domains. Bioinformatic analysis of Mmp10 identified DUF512 (Domain of Unknown Function 512) as a potential Cbl-binding domain in RS enzymes. In this paper, four randomly selected DUF512-containing proteins from various organisms were overexpressed, purified, and shown to bind Cbl. X-ray crystal structures of DUF512-containing proteins from and were determined, confirming their C-terminal Cbl-binding domains. The structure of the DUF512-containing protein from is the first of an RS enzyme containing a PDZ domain. Its RS domain has an unprecedented βα core, whereas most RS enzymes adopt a (βα) core. The DUF512-containing protein from has no PDZ domain, but its RS domain also has an uncommon (βα) core.

PubMed: 39712206
DOI: 10.1021/acsbiomedchemau.4c00067

Experimental method

X-RAY DIFFRACTION (1.96 Å)