DB code: S00518

RLCP classification 1.13.30000.44 : Hydrolysis
CATH domain 3.90.70.10 : Cathepsin B; Chain A Catalytic domain
E.C. 3.4.22.15
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.90.70.10 : Cathepsin B; Chain A S00444 S00445 S00447 S00448 S00449 S00450 S00451 S00446

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Contains RefSeq MEROPS Pfam
P07711 Cathepsin L1
EC 3.4.22.15
Major excreted protein
MEP
Cathepsin L1 heavy chain
Cathepsin L1 light chain
NP_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)
I29.001 ()
PF08246 (Inhibitor_I29)
PF00112 (Peptidase_C1)
[Graphical View]

KEGG enzyme name
cathepsin L
Aldrichina grahami cysteine proteinase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P07711 CATL1_HUMAN Specificity 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. Dimer of a heavy and a light chain linked by disulfide bonds. Lysosome.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00012 C00017 C00001 C00012 C00017
E.C.
Compound Peptide Protein H2O Peptide Protein
Type peptide/protein peptide/protein H2O peptide/protein peptide/protein
ChEBI 15377
PubChem 22247451
962
1cjlA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1cs8A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1icfA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:PRO_209-GLY_210 (chain I) Unbound Unbound
1icfB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1icfC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:PRO_209-GLY_210 (chain J) Unbound Unbound
1icfD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1mhwA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:BP4-CYS-DAR-TYR-PEA Unbound Unbound Unbound
1mhwB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:BP4-CYS-DAR-TYR-PEA Unbound Unbound Unbound
1mhwC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1mhwD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P07711

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1cjlA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLN 19; ;HIS 163;ASN 187 mutant C25S
1cs8A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLN 19; ;HIS 163;ASN 187 OCS 25(Sulfonic Cys)
1icfA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLN 19;CYS 25;HIS 163 CYS 25
1icfB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 187
1icfC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLN 19;CYS 25;HIS 163 CYS 25
1icfD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 187
1mhwA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLN 19; ;HIS 163 CSW 25(Oxidized Cys)
1mhwB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLN 19; ;HIS 163 CSW 25(Oxidized Cys)
1mhwC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 187
1mhwD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 187

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[6]
Fig.1

References
[1]
Resource
Comments
Medline ID
PubMed ID 3490478
Journal J Biol Chem
Year 1986
Volume 261
Pages 14748-51
Authors Johnson DA, Barrett AJ, Mason RW
Title Cathepsin L inactivates alpha 1-proteinase inhibitor by cleavage in the reactive site region.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 7982933
Journal J Biol Chem
Year 1994
Volume 269
Pages 30238-42
Authors Bromme D, Bonneau PR, Lachance P, Storer AC
Title Engineering the S2 subsite specificity of human cathepsin S to a cathepsin L- and cathepsin B-like specificity.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 8896443
Journal EMBO J
Year 1996
Volume 15
Pages 5492-503
Authors Coulombe R, Grochulski P, Sivaraman J, Menard R, Mort JS, Cygler M
Title Structure of human procathepsin L reveals the molecular basis of inhibition by the prosegment.
Related PDB 1cjl 1cs8
Related UniProtKB P07711
[4]
Resource
Comments
Medline ID
PubMed ID 9141479
Journal FEBS Lett
Year 1997
Volume 407
Pages 47-50
Authors Fujishima A, Imai Y, Nomura T, Fujisawa Y, Yamamoto Y, Sugawara T
Title The crystal structure of human cathepsin L complexed with E-64.
Related PDB
Related UniProtKB P07711
[5]
Resource
Comments
Medline ID
PubMed ID 9694859
Journal J Biol Chem
Year 1998
Volume 273
Pages 21067-76
Authors Cuozzo JW, Tao K, Cygler M, Mort JS, Sahagian GG
Title Lysine-based structure responsible for selective mannose phosphorylation of cathepsin D and cathepsin L defines a common structural motif for lysosomal enzyme targeting.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 10470376
Journal Adv Enzyme Regul
Year 1999
Volume 39
Pages 247-60
Authors Katunuma N, Matsui A, Kakegawa T, Murata E, Asao T, Ohba Y
Title Study of the functional share of lysosomal cathepsins by the development of specific inhibitors.
Related PDB
Related UniProtKB
[7]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10022822
Journal EMBO J
Year 1999
Volume 18
Pages 793-803
Authors Guncar G, Pungercic G, Klemencic I, Turk V, Turk D
Title Crystal 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 PDB 1icf
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 10428479
Journal FEBS Lett
Year 1999
Volume 455
Pages 92-6
Authors Popovic T, Cimerman N, Dolenc I, Ritonja A, Brzin J
Title Cathepsin L is capable of truncating cystatin C of 11 N-terminal amino acids.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 10791909
Journal IUBMB Life
Year 1999
Volume 48
Pages 7-12
Authors Turk D, Guncar G, Turk V
Title The p41 fragment story.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 10727410
Journal Biochem J
Year 2000
Volume 347 Pt 1
Pages 123-9
Authors Portaro FC, Santos AB, Cezari MH, Juliano MA, Juliano L, Carmona E
Title Probing the specificity of cysteine proteinases at subsites remote from the active site: analysis of P4, P3, P2' and P3' variations in extended substrates.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 10806395
Journal Eur J Biochem
Year 2000
Volume 267
Pages 2965-72
Authors Kreusch S, Fehn M, Maubach G, Nissler K, Rommerskirch W, Schilling K, Weber E, Wenz I, Wiederanders B
Title An evolutionarily conserved tripartite tryptophan motif stabilizes the prodomains of cathepsin L-like cysteine proteases.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 10713271
Journal FEBS Lett
Year 2000
Volume 469
Pages 203-7
Authors Guo YL, Kurz U, Schultz JE, Lim CC, Wiederanders B, Schilling K
Title The alpha1/2 helical backbone of the prodomains defines the intrinsic inhibitory specificity in the cathepsin L-like cysteine protease subfamily.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 12123713
Journal Adv Enzyme Regul
Year 2002
Volume 42
Pages 159-72
Authors Katunuma N, Tsuge H, Nukatsuka M, Fukushima M
Title Structure-based development of cathepsin L inhibitors and therapeutic applications for prevention of cancer metastasis and cancer-induced osteoporosis.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 12431059
Journal J Med Chem
Year 2002
Volume 45
Pages 5321-9
Authors Chowdhury SF, Sivaraman J, Wang J, Devanathan G, Lachance P, Qi H, Menard R, Lefebvre J, Konishi Y, Cygler M, Sulea T, Purisima EO
Title Design of noncovalent inhibitors of human cathepsin L. From the 96-residue proregion to optimized tripeptides.
Related PDB 1mhw
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 14511383
Journal Eur J Biochem
Year 2003
Volume 270
Pages 4008-15
Authors Bocock JP, Edgell CJ, Marr HS, Erickson AH
Title Human proteoglycan testican-1 inhibits the lysosomal cysteine protease cathepsin L.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 12568610
Journal J Am Chem Soc
Year 2003
Volume 125
Pages 1508-17
Authors Chiva 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
Title Synthesis and NMR structure of p41icf, a potent inhibitor of human cathepsin L.
Related PDB
Related UniProtKB

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]).

Created Updated
2004-08-24 2010-02-02