Crystal structure of N-acetylornithine transcarbamylase from Xanthomonas campestris: a novel enzyme in a new arginine biosynthetic pathway found in several eubacteria.
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.
Shi
Dashuang
D
Children's Research Institute, Children's National Medical Center, Washington, DC 20010, USA. dshi@cnmcresearch.org <dshi@cnmcresearch.org>
Morizono
Hiroki
H
Yu
Xiaolin
X
Roth
Lauren
L
Caldovic
Ljubica
L
Allewell
Norma M
NM
Malamy
Michael H
MH
Tuchman
Mendel
M
D001665:Binding Sites; D019878:Carboxyl and Carbamoyl Transferases / Q000737:chemistry*; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D008024:Ligands; D008958:Models, Molecular; D009954:Ornithine Carbamoyltransferase / Q000737:chemistry*; D011392:Proline / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D014867:Water / Q000737:chemistry; D016959:Xanthomonas campestris / Q000201:enzymology*
D008024:Ligands; D014867:Water; D011392:Proline; D019878:Carboxyl and Carbamoyl Transferases; C500792:N-acetylornithine transcarbamylase; D009954:Ornithine Carbamoyltransferase