A conserved tyrosine residue of Saccharomyces cerevisiae leukotriene A4 hydrolase stabilizes the transition state of the peptidase activity.
作者： Michael W. Thompson , Erin D. Archer , Carrie E. Romer , Rebecca L. Seipelt
DOI: 10.1016/J.PEPTIDES.2006.02.006
关键词:
摘要: Abstract Saccharomyces cerevisiae leukotriene A 4 hydrolase (LTA4H) is a bifunctional aminopeptidase/epoxide and member of the M1 family metallopeptidases. In order to obtain more thorough understanding aminopeptidase activity enzyme, two conserved tyrosine residues, Tyr244 Tyr456, were altered phenylalanine mutant proteins characterized by determining K M k cat for various amino acid β-naphthylamide substrates. While mutation Tyr456 exhibited minimal effect on catalysis, caused an overall 25–100-fold reduction in catalytic all substrates tested. Furthermore, LTA4H Y244F 40-fold decrease affinity RB-3014, transition state analog inhibitor, implicating stabilization.
elsevier.com
sci-hub.se 参考文章(41)
Lars Stoltze, Markus Schirle, Gerold Schwarz, Christian Schröter, Michael W. Thompson, Louis B. Hersh, Hubert Kalbacher, Stefan Stevanovic, Hans-Georg Rammensee, Hansjörg Schild, Two new proteases in the MHC class I processing pathway Nature Immunology. ,vol. 1, pp. 413- 418 ,(2000) , 10.1038/80852
Susan A. Nadin-Davis, Shirley C. Chang, Site-directed mutagenesis of large plasmids BioTechniques. ,vol. 25, pp. 1014- 1019 ,(1998) , 10.2144/98256ST04
Neil D. Rawlings, Alan J. Barrett, [13] Evolutionary families of metallopeptidases Proteolytic Enzymes: Aspartic and Metallo Peptidases. ,vol. 248, pp. 183- 228 ,(1995) , 10.1016/0076-6879(95)48015-3
Tomoharu Osada, Shiro Ikegami, Keiko Takiguchi-Hayashi, Yukiko Yamazaki, Yuko Katoh-Fukui, Toru Higashinakagawa, Yoshiyuki Sakaki, Takashi Takeuchi, Increased Anxiety and Impaired Pain Response in Puromycin-Sensitive Aminopeptidase Gene-Deficient Mice Obtained by a Mouse Gene-Trap Method The Journal of Neuroscience. ,vol. 19, pp. 6068- 6078 ,(1999) , 10.1523/JNEUROSCI.19-14-06068.1999
L. Orning, J.K. Gierse, F.A. Fitzpatrick, The bifunctional enzyme leukotriene-A4 hydrolase is an arginine aminopeptidase of high efficiency and specificity. Journal of Biological Chemistry. ,vol. 269, pp. 11269- 11273 ,(1994) , 10.1016/S0021-9258(19)78120-4
S H Wilkes, J M Prescott, The slow, tight binding of bestatin and amastatin to aminopeptidases. Journal of Biological Chemistry. ,vol. 260, pp. 13154- 13162 ,(1985) , 10.1016/S0021-9258(17)38851-8
L Orning, J Gierse, K Duffin, G Bild, G Krivi, F.A. Fitzpatrick, Mechanism-based inactivation of leukotriene A4 hydrolase/aminopeptidase by leukotriene A4. Mass spectrometric and kinetic characterization. Journal of Biological Chemistry. ,vol. 267, pp. 22733- 22739 ,(1992) , 10.1016/S0021-9258(18)50009-0
M.F. Browner, W.W. Smith, A.L. Castelhano, MATRILYSIN COMPLEXED WITH CARBOXYLATE INHIBITOR Biochemistry. ,vol. 34, pp. 6602- 6610 ,(1996) , 10.2210/PDB1MMP/PDB
Marjolein M.G.M. Thunnissen, Pär Nordlund, Jesper Z. Haeggström, Crystal structure of human leukotriene A(4) hydrolase, a bifunctional enzyme in inflammation. Nature Structural & Molecular Biology. ,vol. 8, pp. 131- 135 ,(2001) , 10.1038/84117
N D Rawlings, A J Barrett, Evolutionary families of peptidases Biochemical Journal. ,vol. 290, pp. 205- 218 ,(1993) , 10.1042/BJ2900205