EzCatDB: S00518
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DB codeS00518
RLCP classification1.13.30000.44 : Hydrolysis
CATH domainDomain 13.90.70.10 : Cathepsin B; Chain ACatalytic domain
E.C.3.4.22.15

CATH domainRelated DB codes (homologues)
3.90.70.10 : Cathepsin B; Chain AS00444,S00445,S00447,S00448,S00449,S00450,S00451,S00446

Enzyme Name
UniProtKBKEGG

P07711
Protein nameCathepsin L1cathepsin L
Aldrichina grahami cysteine proteinase
SynonymsEC 3.4.22.15
Major excreted protein
MEP
ContainsCathepsin L1 heavy chain
Cathepsin L1 light chain
RefSeqNP_001244900.1 (Protein)
NM_001257971.1 (DNA/RNA sequence)
NP_001244901.1 (Protein)
NM_001257972.1 (DNA/RNA sequence)
NP_001903.1 (Protein)
NM_001912.4 (DNA/RNA sequence)
NP_666023.1 (Protein)
NM_145918.2 (DNA/RNA sequence)
PfamPF08246 (Inhibitor_I29)
PF00112 (Peptidase_C1)
[Graphical view]


UniProtKB:Accession NumberP07711
Entry nameCATL1_HUMAN
ActivitySpecificity close to that of papain. As compared to cathepsin B, cathepsin L exhibits higher activity toward protein substrates, but has little activity on Z-Arg-Arg- NHMec, and no peptidyl-dipeptidase activity.
SubunitDimer of a heavy and a light chain linked by disulfide bonds.
Subcellular locationLysosome.
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProducts
KEGG-idC00012C00017C00001C00012C00017
CompoundPeptideProteinH2OPeptideProtein
Typepeptide/proteinpeptide/proteinH2Opeptide/proteinpeptide/protein
ChEBI

15377


PubChem

962
22247451


             
1cjlAUnboundUnbound UnboundUnbound
1cs8AUnboundUnbound UnboundUnbound
1icfAUnboundBound:PRO 209-GLY 210(chain I) UnboundUnbound
1icfBUnboundUnbound UnboundUnbound
1icfCUnboundBound:PRO 209-GLY 210(chain J) UnboundUnbound
1icfDUnboundUnbound UnboundUnbound
1mhwAAnalogue:BP4-CYS-DAR-TYR-PEAUnbound UnboundUnbound
1mhwBAnalogue:BP4-CYS-DAR-TYR-PEAUnbound UnboundUnbound
1mhwCUnboundUnbound UnboundUnbound
1mhwDUnboundUnbound UnboundUnbound

Active-site residues
resource
Swiss-prot;P07711
pdbCatalytic residuesModified residuesMain-chain involved in catalysiscomment
            
1cjlAGLN 19;      ;HIS 163;ASN 187
 
 
mutant C25S
1cs8AGLN 19;      ;HIS 163;ASN 187
OCS 25(Sulfonic Cys)
 
 
1icfAGLN 19;CYS 25;HIS 163        
 
CYS 25
 
1icfB                      ASN 187
 
 
 
1icfCGLN 19;CYS 25;HIS 163        
 
CYS 25
 
1icfD                      ASN 187
 
 
 
1mhwAGLN 19;      ;HIS 163        
CSW 25(Oxidized Cys)
 
 
1mhwBGLN 19;      ;HIS 163        
CSW 25(Oxidized Cys)
 
 
1mhwC                      ASN 187
 
 
 
1mhwD                      ASN 187
 
 
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[6]Fig.1

references
[1]
PubMed ID3490478
JournalJ Biol Chem
Year1986
Volume261
Pages14748-51
AuthorsJohnson DA, Barrett AJ, Mason RW
TitleCathepsin L inactivates alpha 1-proteinase inhibitor by cleavage in the reactive site region.
[2]
PubMed ID7982933
JournalJ Biol Chem
Year1994
Volume269
Pages30238-42
AuthorsBromme D, Bonneau PR, Lachance P, Storer AC
TitleEngineering the S2 subsite specificity of human cathepsin S to a cathepsin L- and cathepsin B-like specificity.
[3]
PubMed ID8896443
JournalEMBO J
Year1996
Volume15
Pages5492-503
AuthorsCoulombe R, Grochulski P, Sivaraman J, Menard R, Mort JS, Cygler M
TitleStructure of human procathepsin L reveals the molecular basis of inhibition by the prosegment.
Related PDB1cjl,1cs8
Related UniProtKBP07711
[4]
PubMed ID9141479
JournalFEBS Lett
Year1997
Volume407
Pages47-50
AuthorsFujishima A, Imai Y, Nomura T, Fujisawa Y, Yamamoto Y, Sugawara T
TitleThe crystal structure of human cathepsin L complexed with E-64.
Related UniProtKBP07711
[5]
PubMed ID9694859
JournalJ Biol Chem
Year1998
Volume273
Pages21067-76
AuthorsCuozzo JW, Tao K, Cygler M, Mort JS, Sahagian GG
TitleLysine-based structure responsible for selective mannose phosphorylation of cathepsin D and cathepsin L defines a common structural motif for lysosomal enzyme targeting.
[6]
PubMed ID10470376
JournalAdv Enzyme Regul
Year1999
Volume39
Pages247-60
AuthorsKatunuma N, Matsui A, Kakegawa T, Murata E, Asao T, Ohba Y
TitleStudy of the functional share of lysosomal cathepsins by the development of specific inhibitors.
[7]
CommentsX-ray crystallography
PubMed ID10022822
JournalEMBO J
Year1999
Volume18
Pages793-803
AuthorsGuncar G, Pungercic G, Klemencic I, Turk V, Turk D
TitleCrystal structure of MHC class II-associated p41 Ii fragment bound to cathepsin L reveals the structural basis for differentiation between cathepsins L and S.
Related PDB1icf
[8]
PubMed ID10428479
JournalFEBS Lett
Year1999
Volume455
Pages92-6
AuthorsPopovic T, Cimerman N, Dolenc I, Ritonja A, Brzin J
TitleCathepsin L is capable of truncating cystatin C of 11 N-terminal amino acids.
[9]
PubMed ID10791909
JournalIUBMB Life
Year1999
Volume48
Pages7-12
AuthorsTurk D, Guncar G, Turk V
TitleThe p41 fragment story.
[10]
PubMed ID10727410
JournalBiochem J
Year2000
Volume347 Pt 1
Pages123-9
AuthorsPortaro FC, Santos AB, Cezari MH, Juliano MA, Juliano L, Carmona E
TitleProbing the specificity of cysteine proteinases at subsites remote from the active site: analysis of P4, P3, P2' and P3' variations in extended substrates.
[11]
PubMed ID10806395
JournalEur J Biochem
Year2000
Volume267
Pages2965-72
AuthorsKreusch S, Fehn M, Maubach G, Nissler K, Rommerskirch W, Schilling K, Weber E, Wenz I, Wiederanders B
TitleAn evolutionarily conserved tripartite tryptophan motif stabilizes the prodomains of cathepsin L-like cysteine proteases.
[12]
PubMed ID10713271
JournalFEBS Lett
Year2000
Volume469
Pages203-7
AuthorsGuo YL, Kurz U, Schultz JE, Lim CC, Wiederanders B, Schilling K
TitleThe alpha1/2 helical backbone of the prodomains defines the intrinsic inhibitory specificity in the cathepsin L-like cysteine protease subfamily.
[13]
PubMed ID12123713
JournalAdv Enzyme Regul
Year2002
Volume42
Pages159-72
AuthorsKatunuma N, Tsuge H, Nukatsuka M, Fukushima M
TitleStructure-based development of cathepsin L inhibitors and therapeutic applications for prevention of cancer metastasis and cancer-induced osteoporosis.
[14]
PubMed ID12431059
JournalJ Med Chem
Year2002
Volume45
Pages5321-9
AuthorsChowdhury SF, Sivaraman J, Wang J, Devanathan G, Lachance P, Qi H, Menard R, Lefebvre J, Konishi Y, Cygler M, Sulea T, Purisima EO
TitleDesign of noncovalent inhibitors of human cathepsin L. From the 96-residue proregion to optimized tripeptides.
Related PDB1mhw
[15]
PubMed ID14511383
JournalEur J Biochem
Year2003
Volume270
Pages4008-15
AuthorsBocock JP, Edgell CJ, Marr HS, Erickson AH
TitleHuman proteoglycan testican-1 inhibits the lysosomal cysteine protease cathepsin L.
[16]
PubMed ID12568610
JournalJ Am Chem Soc
Year2003
Volume125
Pages1508-17
AuthorsChiva C, Barthe P, Codina A, Gairi M, Molina F, Granier C, Pugniere M, Inui T, Nishio H, Nishiuchi Y, Kimura T, Sakakibara S, Albericio F, Giralt E
TitleSynthesis and NMR structure of p41icf, a potent inhibitor of human cathepsin L.

comments
This enzyme belongs to the peptidase family-C1.
This enzyme is composed of two chains, heavy and light chains, which are linked by disulfide bonds. Cleavage and dissociation of the propeptide sequence (Swiss-prot;P07711) leads to the dimerization of the two chains (see [3]).
This enzyme has a similar catalytic mechanism to that of cathepsin B (S00445). The oxyanion hole is composed of the sidechain of Gln19 and the mainchain of Cys25 (see [6]).

createdupdated
2004-08-242010-02-02


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Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
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