EzCatDB: S00445
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DB codeS00445
RLCP classification1.13.30000.44 : Hydrolysis
CATH domainDomain 13.90.70.10 : Cathepsin B; Chain ACatalytic domain
E.C.3.4.22.1

CATH domainRelated DB codes (homologues)
3.90.70.10 : Cathepsin B; Chain AS00444,S00447,S00448,S00449,S00450,S00451,S00446,S00518

Enzyme Name
UniProtKBKEGG

P00787P07858
Protein nameCathepsin BCathepsin Bcathepsin B
cathepsin B1 (obsolete)
cathepsin II
SynonymsEC 3.4.22.1
Cathepsin B1
RSG-2
EC 3.4.22.1
Cathepsin B1
APP secretase
APPS
ContainsCathepsin B light chain
Cathepsin B heavy chain
Cathepsin B light chain
Cathepsin B heavy chain
RefSeq
NP_001899.1 (Protein)
NM_001908.3 (DNA/RNA sequence)
NP_680090.1 (Protein)
NM_147780.2 (DNA/RNA sequence)
NP_680091.1 (Protein)
NM_147781.2 (DNA/RNA sequence)
NP_680092.1 (Protein)
NM_147782.2 (DNA/RNA sequence)
NP_680093.1 (Protein)
NM_147783.2 (DNA/RNA sequence)
MEROPSC01.060 (Cysteine)
C01.060 (Cysteine)
PfamPF00112 (Peptidase_C1)
PF08127 (Propeptide_C1)
[Graphical view]
PF00112 (Peptidase_C1)
PF08127 (Propeptide_C1)
[Graphical view]


UniProtKB:Accession NumberP00787P07858
Entry nameCATB_RATCATB_HUMAN
ActivityHydrolysis of proteins with broad specificity for peptide bonds. Preferentially cleaves -Arg-Arg-|-Xaa bonds in small molecule substrates (thus differing from cathepsin L). In addition to being an endopeptidase, shows peptidyl-dipeptidase activity, liberating C-terminal dipeptides.Hydrolysis of proteins with broad specificity for peptide bonds. Preferentially cleaves -Arg-Arg-|-Xaa bonds in small molecule substrates (thus differing from cathepsin L). In addition to being an endopeptidase, shows peptidyl-dipeptidase activity, liberating C-terminal dipeptides.
SubunitDimer of a heavy chain and a light chain cross-linked by a disulfide bond.Dimer of a heavy chain and a light chain cross-linked by a disulfide bond.
Subcellular locationLysosome. Melanosome (By similarity).Lysosome. Melanosome. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV.
Cofactor


Compound table: links to PDB-related databases & PoSSuM

SubstratesProductsintermediates
KEGG-idC00017C00012C00001C00017C00012I00153I00154I00155
CompoundProteinPeptideH2OProteinPeptidePeptidyl-Cys-tetrahedral-intermediate (with previous peptide)Acyl-enzyme(Peptidyl-Cys-acyl group)Peptidyl-Cys-tetrahedral-intermediate
Typepeptide/proteinpeptide/proteinH2Opeptide/proteinpeptide/protein


ChEBI

15377





PubChem

962
22247451





                
1cpjAUnboundUnbound UnboundUnboundUnboundUnboundUnbound
1cpjBUnboundUnbound UnboundUnboundUnboundUnboundUnbound
1csbAUnboundUnbound UnboundUnboundIntermediate-analogue:EP0UnboundUnbound
1csbBUnboundUnbound UnboundUnboundUnboundUnboundUnbound
1csbDUnboundUnbound UnboundUnboundIntermediate-analogue:EP0UnboundUnbound
1csbEUnboundUnbound UnboundUnboundUnboundUnboundUnbound
1cteAUnboundUnbound UnboundUnboundUnboundIntermediate-analogue:PYSUnbound
1cteBUnboundUnbound UnboundUnboundUnboundIntermediate-analogue:PYSUnbound
1hucAUnboundUnbound UnboundUnboundUnboundUnboundUnbound
1hucBUnboundUnbound UnboundUnboundUnboundUnboundUnbound
1hucCUnboundUnbound UnboundUnboundUnboundUnboundUnbound
1hucDUnboundUnbound UnboundUnboundUnboundUnboundUnbound
1mirAUnboundUnbound UnboundUnboundUnboundUnboundUnbound
1mirBUnboundUnbound UnboundUnboundUnboundUnboundUnbound
1qdqAUnboundUnbound UnboundUnboundIntermediate-analogue:074 Unbound
1theAUnboundUnbound UnboundUnboundUnboundIntermediate-analogue:0E6Unbound
1theBUnboundUnbound UnboundUnboundUnboundIntermediate-analogue:0E6Unbound
3pbhAUnboundUnbound UnboundUnboundUnboundUnboundUnbound

Active-site residues
pdbCatalytic residuesMain-chain involved in catalysiscomment
           
1cpjAGLN 23;CYS 29;HIS 199;ASN 219
CYS 29
 
1cpjBGLN 23;CYS 29;HIS 199;ASN 219
CYS 29
 
1csbAGLN 23;CYS 29                
CYS 29
 
1csbB              HIS 199;ASN 219
 
 
1csbDGLN 23;CYS 29                
CYS 29
 
1csbE              HIS 199;ASN 219
 
 
1cteAGLN 23;CYS 29;HIS 199;ASN 219
CYS 29
 
1cteBGLN 23;CYS 29;HIS 199;ASN 219
CYS 29
 
1hucAGLN 23;CYS 29                
CYS 29
 
1hucB              HIS 199;ASN 219
 
 
1hucCGLN 23;CYS 29                
CYS 29
 
1hucD              HIS 199;ASN 219
 
 
1mirAGLN 23;      ;HIS 199;ASN 219
      
mutant C29S
1mirBGLN 23;      ;HIS 199;ASN 219
      
mutant C29S
1qdqAGLN 23;CYS 29;HIS 199;ASN 219
CYS 29
 
1theAGLN 23;CYS 29;HIS 199;ASN 219
CYS 29
 
1theBGLN 23;CYS 29;HIS 199;ASN 219
CYS 29
 
3pbhAGLN 23;CYS 29;HIS 199;ASN 219
CYS 29
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]p.2327-2328
[2]p.4720-4721
[4]p.5530-5532, Fig.7
[8]p.781

references
[1]
CommentsX-ray crystallography (2.15 Angstroms)
PubMed ID1868826
JournalEMBO J
Year1991
Volume10
Pages2321-30
AuthorsMusil D, Zucic D, Turk D, Engh RA, Mayr I, Huber R, Popovic T, Turk V, Towatari T, Katunuma N, et al
TitleThe refined 2.15 A X-ray crystal structure of human liver cathepsin B: the structural basis for its specificity.
Related PDB1huc
[2]
PubMed ID1537854
JournalJ Biol Chem
Year1992
Volume267
Pages4713-21
AuthorsHasnain S, Hirama T, Tam A, Mort JS
TitleCharacterization of recombinant rat cathepsin B and nonglycosylated mutants expressed in yeast. New insights into the pH dependence of cathepsin B-catalyzed hydrolyses.
[3]
CommentsX-ray crystallography (2.0 Angstroms, with inhibitor)
PubMed ID7718586
JournalBiochemistry
Year1995
Volume34
Pages4791-7
AuthorsTurk D, Podobnik M, Popovic T, Katunuma N, Bode W, Huber R, Turk V
TitleCrystal structure of cathepsin B inhibited with CA030 at 2.0-A resolution: A basis for the design of specific epoxysuccinyl inhibitors.
Related PDB1csb
[4]
CommentsX-ray crystallography
PubMed ID7890671
JournalJ Biol Chem, Erratum in:J Biol Chem 1995 Nov 24;270(47):28494
Year1995
Volume270
Pages5527-33
AuthorsJia Z, Hasnain S, Hirama T, Lee X, Mort JS, To R, Huber CP
TitleCrystal structures of recombinant rat cathepsin B and a cathepsin B-inhibitor complex. Implications for structure-based inhibitor design.
Related PDB1cpj,1cte,1the
[5]
CommentsX-ray crystallography (3.2-3.3 Angstroms)
PubMed ID8617355
JournalFEBS Lett
Year1996
Volume384
Pages211-4
AuthorsTurk D, Podobnik M, Kuhelj R, Dolinar M, Turk V
TitleCrystal structures of human procathepsin B at 3.2 and 3.3 Angstroms resolution reveal an interaction motif between a papain-like cysteine protease and its propeptide.
Related PDB3pbh
[6]
CommentsX-ray crystallography (2.8 Angstroms)
PubMed ID8740363
JournalStructure
Year1996
Volume4
Pages405-16
AuthorsCygler M, Sivaraman J, Grochulski P, Coulombe R, Storer AC, Mort JS
TitleStructure of rat procathepsin B: model for inhibition of cysteine protease activity by the proregion.
Related PDB1mir
[7]
PubMed ID9233788
JournalEMBO J
Year1997
Volume16
Pages3787-96
AuthorsJohnston SC, Larsen CN, Cook WJ, Wilkinson KD, Hill CP
TitleCrystal structure of a deubiquitinating enzyme (human UCH-L3) at 1.8 A resolution.
[8]
CommentsX-ray crystallography (2.5 Angstroms)
Medline ID97446326
PubMed ID9299326
JournalJ Mol Biol
Year1997
Volume271
Pages774-788
AuthorsPodobnik M., Kuhelj R., Turk V., Turk D
TitleCrystal structure of the wild-type human procathepsin B at 2.5-A resolution reveals the native active site of a papain-like cysteine protease zymogen.
Related UniProtKBP07858
[9]
Comments(catalysis)
PubMed ID10213604
JournalBiochemistry
Year1999
Volume38
Pages5017-23
AuthorsQuraishi O, Nagler DK, Fox T, Sivaraman J, Cygler M, Mort JS, Storer AC
TitleThe occluding loop in cathepsin B defines the pH dependence of inhibition by its propeptide.
[10]
Commentscatalysis
PubMed ID9890884
JournalBiochemistry
Year1999
Volume38
Pages73-80
AuthorsLukong KE, Elsliger MA, Mort JS, Potier M, Pshezhetsky AV
TitleIdentification of UDP-N-acetylglucosamine-phosphotransferase-binding sites on the lysosomal proteases, cathepsins A, B, and D.
[11]
CommentsX-ray crystallography (2.18 Angstroms)
PubMed ID10739956
JournalJ Biochem (Tokyo)
Year2000
Volume127
Pages635-43
AuthorsYamamoto A, Tomoo K, Hara T, Murata M, Kitamura K, Ishida T
TitleSubstrate specificity of bovine cathepsin B and its inhibition by CA074, based on crystal structure refinement of the complex.
Related PDB1qdq

comments
This enzyme belongs to the peptidase family-C1.
According to the literature [1], the sidechain of Cys29 is reactive, with pKa 3.4, to form covalent bond with substrate during the first acylation step. This residue is positioned to form a hydrogen bond with the imidazole ring of the catalytic His199, which, in turn, forms a hydrogen bond with Asn219 [1]. The biochemical data [2] indicated that the pKa of His199 is 8.6, which is comparable to that of about 8.3 for the acitive site His159 of papain. Thus, this histidine residue must stabilize the thiolate anion with its positive charge [2].
The oxyanion hole, composed of Gln23 sidechain and Cys29 mainchain amide groups, is thought to stabilize the tetrahedral intermediate (see [4] & [8]).

createdupdated
2002-07-012012-10-23


Copyright: Nozomi Nagano, JST & CBRC-AIST
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Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
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Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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