3B1D

Crystal structure of betaC-S lyase from Streptococcus anginosus in complex with L-serine: External aldimine form

Summary for 3B1D

• Entry DOI: 10.2210/pdb3b1d/pdb
• Related: 3B1C 3B1E
• Descriptor: BetaC-S lyase, PYRIDOXAL-5'-PHOSPHATE, [3-HYDROXY-2-METHYL-5-PHOSPHONOOXYMETHYL-PYRIDIN-4-YLMETHYL]-SERINE, ... (6 entities in total)
• Functional Keywords: lyase
• Biological source: Streptococcus anginosus
• Total number of polymer chains: 4
• Total formula weight: 183149.78

Authors

Kezuka, Y.,Yoshida, Y.,Nonaka, T. (deposition date: 2011-06-29, release date: 2012-06-27, Last modification date: 2017-10-11)

Primary citation

Kezuka, Y.,Yoshida, Y.,Nonaka, T.
Structural insights into catalysis by beta C-S lyase from Streptococcus anginosus
Proteins, 80:2447-2458, 2012

PubMed Abstract: Hydrogen sulfide (H(2)S) is a causative agent of oral malodor and may play an important role in the pathogenicity of oral bacteria such as Streptococcus anginosus. In this microorganism, H(2)S production is associated with βC-S lyase (Lcd) encoded by lcd gene, which is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that catalyzes the α,β-elimination of sulfur-containing amino acids. When Lcd acts on L-cysteine, H(2)S is produced along with pyruvate and ammonia. To understand the H(2)S-producing mechanism of Lcd in detail, we determined the crystal structures of substrate-free Lcd (internal aldimine form) and two reaction intermediate complexes (external aldimine and α-aminoacrylate forms). The formation of intermediates induced little changes in the overall structure of the enzyme and in the active site residues, with the exception of Lys234, a PLP-binding residue. Structural and mutational analyses highlighted the importance of the active site residues Tyr60, Tyr119, and Arg365. In particular, Tyr119 forms a hydrogen bond with the side chain oxygen atom of L-serine, a substrate analog, in the external aldimine form suggesting its role in the recognition of the sulfur atom of the true substrate (L-cysteine). Tyr119 also plays a role in fixing the PLP cofactor at the proper position during catalysis through binding with its side chain. Finally, we partly modified the catalytic mechanism known for cystalysin, a βC-S lyase from Treponema denticola, and proposed an improved mechanism, which seems to be common to the βC-S lyases from oral bacteria.

PubMed: 22674431
DOI: 10.1002/prot.24129

Experimental method

X-RAY DIFFRACTION (1.66 Å)