W0100

Crystal Structure of L-homocysteine γ-lyase at 1.8 Å. Tom Allen, Vandana Prasad, G. Sridhar Prasad, Qinghong Han, Mingxu Xu, Yuying Tan, Robert Hoffman, Ramaswamy S., Dept. of Biochemistry, Univ. of Iowa, 51 Newton Rd., Iowa City, IA 52242 USA.

Numerous malignant cell lines, including those responsible for some gastric and colon cancers, have an elevated dependence on methionine relative to ordinary cells. Treatment of these cancers with enzymes that reduce free methionine has been shown to slow or arrest tumor growth. When deprived of methionine, cells can synthesize it from the similar amino acid homocysteine. We have recently solved the structure of the enzyme L-homocysteine α,γ-hydrolase (obtained from Trichomonas vaginalis) which degrades homocysteine. The structure of homocysteinase is similar to that of other α,γ-hydrolases such L-methionine α,γ-hydrolase. In conjunction with methioninase, homocysteinase is expected to enhance cancer treatment, especially if its activity and half-life can be increased by mutation. Further investigation of the interactions involved, such as the binding of pyridoxal 5’ phosphate (PLP), will help elucidate the mechanisms of this type of enzyme.