7VUA

Anaerobic hydroxyproline degradation involving C-N cleavage by a glycyl radical enzyme

Summary for 7VUA

• Entry DOI: 10.2210/pdb7vua/pdb
• Descriptor: HplG, (4S)-4-hydroxy-D-proline (3 entities in total)
• Functional Keywords: c-n-lyase, lyase
• Biological source: Clostridiales bacterium
• Total number of polymer chains: 2
• Total formula weight: 178205.62

Authors

Duan, Y.,Lu, Q.,Yuchi, Z.,Zhang, Y. (deposition date: 2021-11-01, release date: 2022-06-01, Last modification date: 2024-04-03)

Primary citation

Duan, Y.,Wei, Y.,Xing, M.,Liu, J.,Jiang, L.,Lu, Q.,Liu, X.,Liu, Y.,Ang, E.L.,Liao, R.Z.,Yuchi, Z.,Zhao, H.,Zhang, Y.
Anaerobic Hydroxyproline Degradation Involving C-N Cleavage by a Glycyl Radical Enzyme.
J.Am.Chem.Soc., 144:9715-9722, 2022

PubMed Abstract: Hydroxyprolines are highly abundant in nature as they are components of many structural proteins and osmolytes. Anaerobic degradation of -4-hydroxy-l-proline (t4L-HP) was previously found to involve the glycyl radical enzyme (GRE) t4L-HP dehydratase (HypD). Here, we report a pathway for anaerobic hydroxyproline degradation that involves a new GRE, -4-hydroxy-d-proline (t4D-HP) C-N-lyase (HplG). In this pathway, -4-hydroxy-l-proline (c4L-HP) is first isomerized to t4D-HP, followed by radical-mediated ring opening by HplG to give 2-amino-4-ketopentanoate (AKP), the first example of a ring opening reaction catalyzed by a GRE 1,2-eliminase. Subsequent cleavage by AKP thiolase (OrtAB) yields acetyl-CoA and d-alanine. We report a crystal structure of HplG in complex with t4D-HP at a resolution of 2.7 Å, providing insights into its catalytic mechanism. Different from HypD commonly identified in proline-reducing Clostridia, HplG is present in other types of fermenting bacteria, including propionate-producing bacteria, underscoring the diversity of enzymatic radical chemistry in the anaerobic microbiome.

PubMed: 35611954
DOI: 10.1021/jacs.2c01673

Experimental method

X-RAY DIFFRACTION (2.695 Å)