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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
9
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pubmed:dateCreated |
1991-9-18
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pubmed:abstractText |
From the lysosomal cysteine proteinase cathepsin B, isolated from human liver in its two-chain form, monoclinic crystals were obtained which contain two molecules per asymmetric unit. The molecular structure was solved by a combination of Patterson search and heavy atom replacement methods (simultaneously with rat cathepsin B) and refined to a crystallographic R value of 0.164 using X-ray data to 2.15 A resolution. The overall folding pattern of cathepsin B and the arrangement of the active site residues are similar to the related cysteine proteinases papain, actinidin and calotropin DI. 166 alpha-carbon atoms out of 248 defined cathepsin B residues are topologically equivalent (with an r.m.s. deviation of 1.04 A) with alpha-carbon atoms of papain. However, several large insertion loops are accommodated on the molecular surface and modify its properties. The disulphide connectivities recently determined for bovine cathepsin B by chemical means were shown to be correct. Some of the primed subsites are occluded by a novel insertion loop, which seems to favour binding of peptide substrates with two residues carboxy-terminal to the scissile peptide bond; two histidine residues (His110 and His111) in this "occluding loop' provide positively charged anchors for the C-terminal carboxylate group of such polypeptide substrates. These structural features explain the well-known dipeptidyl carboxypeptidase activity of cathepsin B. The other subsites adjacent to the reactive site Cys29 are relatively similar to papain; Glu245 in the S2 subsite favours basic P2-side chains. The above mentioned histidine residues, but also the buried Glu171 might represent the group with a pKa of approximately 5.5 near the active site, which governs endo- and exopeptidase activity. The "occluding loop' does not allow cystatin-like protein inhibitors to bind to cathepsin B as they do to papain, consistent with the reduced affinity of these protein inhibitors for cathepsin B compared with the related plant enzymes.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-1165251,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-2103490,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-2180938,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-2226854,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-2347312,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-2390214,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-2397208,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-2400573,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-2407065,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-3010323,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-3191914,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-3202963,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-3312190,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-3318552,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-3360126,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-3379063,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-3463996,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-3522589,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-3530135,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-3675577,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-3889350,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-3890831,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-3972105,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-4004778,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-42540,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-6035483,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-6388564,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-6502713,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-6574504,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-6667333,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-6721883,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-6746670,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-6847195,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-7003158,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-7043200,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-7044372,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-7342602,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-7458901,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-7462205,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1868826-952885
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0261-4189
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
10
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pubmed:owner |
NLM
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pubmed:authorsComplete |
N
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pubmed:pagination |
2321-30
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:1868826-Amino Acid Sequence,
pubmed-meshheading:1868826-Binding Sites,
pubmed-meshheading:1868826-Cathepsin B,
pubmed-meshheading:1868826-Crystallization,
pubmed-meshheading:1868826-Cysteine Endopeptidases,
pubmed-meshheading:1868826-Humans,
pubmed-meshheading:1868826-Liver,
pubmed-meshheading:1868826-Molecular Sequence Data,
pubmed-meshheading:1868826-Papain,
pubmed-meshheading:1868826-Peptides,
pubmed-meshheading:1868826-Protein Conformation,
pubmed-meshheading:1868826-Sequence Homology, Nucleic Acid,
pubmed-meshheading:1868826-Substrate Specificity,
pubmed-meshheading:1868826-X-Ray Diffraction
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pubmed:year |
1991
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pubmed:articleTitle |
The refined 2.15 A X-ray crystal structure of human liver cathepsin B: the structural basis for its specificity.
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pubmed:affiliation |
Max-Planck-Institut für Biochemie, Martinsried, FRG.
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pubmed:publicationType |
Journal Article,
Comparative Study
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