Abstract: Bacterial L-asparaginases catalyzing hydrolysis of L-asparagine up to L-aspartate and ammonia, are used in medical practice for treatment of acute lymphoblastic leukemia. The long-term therapy with these preparations is accompanied by a number of side effects, which are attributed to glutaminase activity of L-asparaginase. Substrate specificity and activity of L-asparaginases are directly associated with the process of enzyme oligomerization. It is active only in the tetrameric form as the active sites are located in contact areas between monomers. The present work is devoted to homology modeling of spatial structure of L-asparaginase from Erwinia carotovora, the comparative molecular-graphic analysis of subunits interfaces, as well as development of experimental approach for enzyme oligomerization study. L-asparaginase was immobilized on a CM5 chip surface of optical biosensor Biacore 3000 based on the surface plasmon resonance technology. The dissociation process of enzyme tetrameric complexes up to monomers and subsequent oligomerization process have been registered.
9. Muller H.J., Beier R., Loning L., Blutters-Sawatzki R., Dorffel W., Maass E., Muller-Weihrich S., Scheel-Walter H.G., Scherer F., Stahnke K., Schrappe M., Horn A., Lumkemann K., Boos J. (2001) Br. J. Haematol., 114, 794-799. Scholar google search
16. Bell K.S., Sebaihia M., Pritchard L., Holden M.T.G., Hyman L.J., Holeva M.C., Thomson N.R., Bentley S.D., Churcher L.J.C., Mungall K., Atkin R., Bason N., Brooks K., Chillingworth T., Clark K., Doggett J., Fraser A., Hance Z., Hauser H., , Toth I.K. (2004) Proc. Natl. Acad. Sci. USA, 101, 11105-11110. Scholar google search
33. Jonsson U., Fagerstam L., Ivarsson B., Johnsson B., Karlsson R., Lundh K., Lofas S., Persson B., Roos H., Ronnberg I., Sjolander R., Stenberg E., Stahlberg R., Urbaniczky C., Ostlin H., Malmqvist M. (1991) BioTechniques. 11, 620-627. Scholar google search
34. Кислицын Ю.А., Кравченко О.В., Никонов С.В., Куранова И.П. (2006) Кристаллография, 51. (в печати). Scholar google search