8D27

Arginase Domain of Ornithine Decarboxylase/Arginase from Fusobacterium nucleatum

Summary for 8D27

• Entry DOI: 10.2210/pdb8d27/pdb
• Descriptor: Arginase (2 entities in total)
• Functional Keywords: arginase domain, ornithine decarboxylase/arginase, inactive, oda, hydrolase
• Biological source: Fusobacterium nucleatum subsp. nucleatum ATCC 25586
• Total number of polymer chains: 2
• Total formula weight: 64162.87

Authors

Chan, A.C.,Kolesnikov, M.,Murphy, M.E. (deposition date: 2022-05-27, release date: 2022-07-06, Last modification date: 2024-04-03)

Primary citation

Mothersole, R.G.,Kolesnikov, M.,Chan, A.C.K.,Oduro, E.,Murphy, M.E.P.,Wolthers, K.R.
Sequence Divergence in the Arginase Domain of Ornithine Decarboxylase/Arginase in Fusobacteriacea Leads to Loss of Function in Oral Associated Species.
Biochemistry, 61:1378-1391, 2022

PubMed Abstract: A number of species within the family of Gram-negative bacteria uniquely encode for an ornithine decarboxylase/arginase (ODA) that ostensibly channels l-ornithine generated by hydrolysis of l-arginine to putrescine formation. However, two aspartate residues required for coordination to a catalytically obligatory manganese cluster of arginases are substituted for a serine and an asparagine. Curiously, these natural substitutions occur only in a clade of Fusobacterium species that inhabit the oral cavity. Herein, we expressed and isolated full-length ODA from the opportunistic oral pathogen along with the individual arginase and ornithine decarboxylase components. The crystal structure of the arginase domain reveals that it adopts the classical α/β arginase-fold, but metal ions are absent in the active site. As expected, the ureohydrolase activity with l-arginine was not detected for wild-type ODA or the isolated arginase domain. However, engineering of the complete metal coordination environment through site-directed mutagenesis restored Mn binding capacity and arginase activity, although the catalytic efficiency for l-arginine was low (60-100 M s). Full-length ODA and the isolated ODC component were able to decarboxylate both l-ornithine and l-arginine to form putrescine and agmatine, respectively, but / of l-ornithine was ∼20-fold higher compared to l-arginine. We discuss environmental conditions that may have led to the natural selection of an inactive arginase in the oral associated species of .

PubMed: 35732022
DOI: 10.1021/acs.biochem.2c00197

Experimental method

X-RAY DIFFRACTION (2.25 Å)