HpxW from the ubiquitous pathogen Klebsiella pneumoniae is involved in a novel
uric acid degradation pathway downstream from the formation of oxalurate.
Specifically, HpxW is an oxamate amidohydrolase which catalyzes the conversion
of oxamate to oxalate and is a member of the Ntn-hydrolase superfamily. HpxW is
autoprocessed from an inactive precursor to form a heterodimer, resulting in a
35.5 kDa α subunit and a 20 kDa β subunit. Here, the structure of HpxW is
presented and the substrate complex is modeled. In addition, the steady-state
kinetics of this enzyme and two active-site variants were characterized. These
structural and biochemical studies provide further insight into this class of
enzymes and allow a mechanism for catalysis consistent with other members of the
Ntn-hydrolase superfamily to be proposed.
