5V1X

Carbon Sulfoxide lyase, Egt2 Y134F in complex with its substrate

Summary for 5V1X

• Entry DOI: 10.2210/pdb5v1x/pdb
• Descriptor: Hercynylcysteine sulfoxide lyase, FORMIC ACID, (1S)-2-{2-[(R)-(2R)-2-amino-2-carboxyethanesulfinyl]-1H-imidazol-4-yl}-1-carboxy-N,N,N-trimethylethan-1-aminium, ... (4 entities in total)
• Functional Keywords: c-s lyase, plp dependent, lyase
• Biological source: Neurospora crassa
• Total number of polymer chains: 8
• Total formula weight: 452306.99

Authors

Irani, S.,Zhang, Y. (deposition date: 2017-03-02, release date: 2018-03-07, Last modification date: 2024-05-15)

Primary citation

Irani, S.,Naowarojna, N.,Tang, Y.,Kathuria, K.R.,Wang, S.,Dhembi, A.,Lee, N.,Yan, W.,Lyu, H.,Costello, C.E.,Liu, P.,Zhang, Y.J.
Snapshots of C-S Cleavage in Egt2 Reveals Substrate Specificity and Reaction Mechanism.
Cell Chem Biol, 25:519-529.e4, 2018

PubMed Abstract: Sulfur incorporation in the biosynthesis of ergothioneine, a histidine thiol derivative, differs from other well-characterized transsulfurations. A combination of a mononuclear non-heme iron enzyme-catalyzed oxidative C-S bond formation and a subsequent pyridoxal 5'-phosphate (PLP)-mediated C-S lyase reaction leads to the net transfer of a sulfur atom from a cysteine to a histidine. In this study, we structurally and mechanistically characterized a PLP-dependent C-S lyase Egt2, which mediates the sulfoxide C-S bond cleavage in ergothioneine biosynthesis. A cation-π interaction between substrate and enzyme accounts for Egt2's preference of sulfoxide over thioether as a substrate. Using mutagenesis and structural biology, we captured three distinct states of the Egt2 C-S lyase reaction cycle, including a labile sulfenic intermediate captured in Egt2 crystals. Chemical trapping and high-resolution mass spectrometry were used to confirm the involvement of the sulfenic acid intermediate in Egt2 catalysis.

PubMed: 29503207
DOI: 10.1016/j.chembiol.2018.02.002

Experimental method

X-RAY DIFFRACTION (2.558 Å)