Structure of a Cys25-->Ser mutant of human cathepsin S.
Cathepsin S (EC 3.4.22.27), a cysteine proteinase of the papain superfamily, plays a critical role in the generation of a major histocompatibility complex (MHC) class II restricted T-cell response by antigen-presenting cells. Therefore, selective inhibition of this enzyme may be useful in modulating class II restricted T-cell responses in immune-related disorders such as rheumatoid arthritis, multiple sclerosis and extrinsic asthma. The three-dimensional structure at 2.2 A resolution of the active-site Cys25-->Ser mutant presented here in an unliganded state provides further insight useful for the design of selective enzyme inhibitors.
Turkenburg
Johan P
JP
York Structural Biology Laboratory, Chemistry Department, University of York, Heslington, York YO10 5DD, England.
Lamers
Marieke B A C
MB
Brzozowski
A Marek
AM
Wright
Lisa M
LM
Hubbard
Roderick E
RE
Sturt
Simone L
SL
Williams
David H
DH
D019943:Amino Acid Substitution; D002403:Cathepsins / Q000737:chemistry* / Q000235:genetics; D003460:Crystallization; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry; D012694:Serine / Q000235:genetics
D011994:Recombinant Proteins; D012694:Serine; D002403:Cathepsins; C028217:cathepsin S; D003545:Cysteine