Substrate specificity of bovine cathepsin B and its inhibition by CA074, based on crystal structure refinement of the complex
The crystal structure of the bovine spleen cathepsin B (BSCB)-CA074 complex was refined to R = 0.152 using X-ray diffraction data up to 2.18 A resolution. BSCB is characterized by an extra Cys148-Cys252 disulfide bridge, as compared with rat and human CBs. Although the crystal structures of these en...
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Published in | Journal of biochemistry (Tokyo) Vol. 127; no. 4; pp. 635 - 643 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Oxford University Press
01.04.2000
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Subjects | |
Online Access | Get full text |
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Summary: | The crystal structure of the bovine spleen cathepsin B (BSCB)-CA074 complex was refined to R = 0.152 using X-ray diffraction data up to 2.18 A resolution. BSCB is characterized by an extra Cys148-Cys252 disulfide bridge, as compared with rat and human CBs. Although the crystal structures of these enzymes showed similar overall folding, a difference was observed in the occluding loop, a structural element specific only to CB. Comparison of the torsion angles indicated the different flexibilities of their loop structures. The oxirane C6 atom of CA074 was covalently bonded to the Cys29 Sy atom (C3-Sy=1.81 Å), where the S-configuration was transformed to the R-form. Concerning the oxirane carbon atom that participates in the covalent bonding with the Cys residue, an acceptable rule has been proposed. The substrate specificities at the Sn (n = 1–3) and Sn' (n=1 and 2) subsites of CB, together with the interaction features as to CA074, have been discussed in comparison with the crystal structure of the papain-CA028 (a CA074-related inhibitor) complex. |
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Bibliography: | ark:/67375/HXZ-GPMRWT6F-N 1 To whom correspondence should be addressed. istex:ADE0E4D14639DB6B09996E0D69082DD5A05436D1 ArticleID:127.4.635 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0021-924X 1756-2651 |
DOI: | 10.1093/oxfordjournals.jbchem.a022651 |