9IXE

Crystal structure of Copper-bound N(omega)-hydroxy-L-arginine hydrolase without oxidized Cys86

Replaces:  9IQ9Replaces:  8IUT

Summary for 9IXE

• Entry DOI: 10.2210/pdb9ixe/pdb
• Related: 9IXC 9IXD
• Descriptor: N(omega)-hydroxy-L-arginine amidinohydrolase, MANGANESE (II) ION, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: hydrolase
• Biological source: Streptomyces lavendulae
• Total number of polymer chains: 2
• Total formula weight: 60358.22

Authors

Oda, K.,Matoba, Y. (deposition date: 2024-07-27, release date: 2024-11-20, Last modification date: 2025-01-01)

Primary citation

Oda, K.,Komaguchi, K.,Matoba, Y.
Copper inactivates DcsB by oxidizing the metal ligand Cys86 to sulfinic acid.
Febs J., 291:5486-5505, 2024

PubMed Abstract: N-hydroxy-l-arginine amidinohydrolase (EC:3.5.3.25), an enzyme in the d-cycloserine (d-CS) biosynthetic pathway of Streptomyces lavendulae, catalyzes the hydrolysis of an arginase inhibitor, N-hydroxy-l-arginine, to produce l-ornithine and hydroxyurea, despite being homologous to arginase. Like arginase, the enzyme (DcsB) possesses two manganese ions (Mn and Mn) essential for the enzymatic reaction at the bottom of the cavity formed within the molecule. However, one of the Mn ligands in DcsB is Cys86, whereas the corresponding residues in arginase are histidine. In this study, we determined the crystal structure of Mn-free DcsB to elucidate the installation mechanism of the manganese ions. The flipping of the His111 residue after the formation of the coordination bond to the second manganese ion may facilitate the installation of Mn and the closing of the cavity entrance to retain Mn and Mn at the active site. Copper ions, which are known to be a positive regulator of many secondary metabolites in Streptomyces species, were found to irreversibly inactivate the catalytic activity of DcsB. Mass spectrometric and crystallographic analyses of the Cu(II)-treated DcsB indicated that Cys86 is oxidized to sulfinic acid. The d-CS biosynthesis in the producing microorganism may be negatively regulated by the concentration of intracellular copper ions, which mediates the oxidative stress.

PubMed: 39563074
DOI: 10.1111/febs.17325

Experimental method

X-RAY DIFFRACTION (1.58 Å)