Crystal structure of N-acetylornithine transcarbamylase from Xanthomonas campestris: a novel enzyme in a new arginine biosynthetic pathway found in several eubacteria.

Dashuang Shi, Hiroki Morizono, Xiaolin Yu, Lauren Roth, Ljubica Caldovic, Norma M Allewell, Michael H Malamy, Mendel Tuchman

Index: J. Biol. Chem. 280 , 14366-14369, (2005)

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Abstract

We have identified in Xanthomonas campestris a novel N-acetylornithine transcarbamylase that replaces ornithine transcarbamylase in the canonic arginine biosynthetic pathway of several Eubacteria. The crystal structures of the protein in the presence and absence of the reaction product, N-acetylcitrulline, were determined. This new family of transcarbamylases lacks the DxxSMG motif that is characteristic of all ornithine transcarbamylases (OTCases) and contains a novel proline-rich loop that forms part of the active site. The specificity for N-acetylornithine is conferred by hydrogen bonding with residues in the proline-rich loop via water molecules and by hydrophobic interactions with residues from the adjacent 80's, 120's, and proline-rich loops. This novel protein structure provides a starting point for rational design of specific analogs that may be useful in combating human and plant pathogens that utilize acetylornithine transcarbamylase rather than ornithine transcarbamylase.