3WV9

Guanylylpyridinol (GP)- and ATP-bound HcgE from Methanothermobacter marburgensis

Summary for 3WV9

• Entry DOI: 10.2210/pdb3wv9/pdb
• Related: 3WV7 3WV8 3WVA 3WVB 3WVC
• Descriptor: Hmd co-occurring protein HcgE, ADENOSINE-5'-TRIPHOSPHATE, 5'-O-[(S)-{[2-(carboxymethyl)-6-hydroxy-3,5-dimethylpyridin-4-yl]oxy}(hydroxy)phosphoryl]guanosine, ... (5 entities in total)
• Functional Keywords: e1 enzyme superfamily, uba/thif-type nad/fad binding fold, adenylyltransferase, atp binding, transferase
• Biological source: Methanothermobacter marburgensis
• Total number of polymer chains: 4
• Total formula weight: 99473.53

Authors

Fujishiro, T.,Ermler, U.,Shima, S. (deposition date: 2014-05-16, release date: 2015-04-29, Last modification date: 2023-11-08)

Primary citation

Fujishiro, T.,Kahnt, J.,Ermler, U.,Shima, S.
Protein-pyridinol thioester precursor for biosynthesis of the organometallic acyl-iron ligand in [Fe]-hydrogenase cofactor
Nat Commun, 6:6895-6895, 2015

PubMed Abstract: The iron-guanylylpyridinol (FeGP) cofactor of [Fe]-hydrogenase contains a prominent iron centre with an acyl-Fe bond and is the only acyl-organometallic iron compound found in nature. Here, we identify the functions of HcgE and HcgF, involved in the biosynthesis of the FeGP cofactor using structure-to-function strategy. Analysis of the HcgE and HcgF crystal structures with and without bound substrates suggest that HcgE catalyses the adenylylation of the carboxy group of guanylylpyridinol (GP) to afford AMP-GP, and subsequently HcgF catalyses the transesterification of AMP-GP to afford a Cys (HcgF)-S-GP thioester. Both enzymatic reactions are confirmed by in vitro assays. The structural data also offer plausible catalytic mechanisms. This strategy of thioester activation corresponds to that used for ubiquitin activation, a key event in the regulation of multiple cellular processes. It further implicates a nucleophilic attack onto the acyl carbon presumably via an electron-rich Fe(0)- or Fe(I)-carbonyl complex in the Fe-acyl formation.

PubMed: 25882909
DOI: 10.1038/ncomms7895

Experimental method

X-RAY DIFFRACTION (2.75 Å)