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 15377
PubChem			22247451 962 22247451 962

1cjlA	Unbound	Unbound		Unbound	Unbound
1cs8A	Unbound	Unbound		Unbound	Unbound
1icfA	Unbound	Bound:PRO_209-GLY_210 (chain I)		Unbound	Unbound
1icfB	Unbound	Unbound		Unbound	Unbound
1icfC	Unbound	Bound:PRO_209-GLY_210 (chain J)		Unbound	Unbound
1icfD	Unbound	Unbound		Unbound	Unbound
1mhwA	Analogue:BP4-CYS-DAR-TYR-PEA	Unbound		Unbound	Unbound
1mhwB	Analogue:BP4-CYS-DAR-TYR-PEA	Unbound		Unbound	Unbound
1mhwC	Unbound	Unbound		Unbound	Unbound
1mhwD	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	GLN 19; ;HIS 163;ASN 187				mutant C25S
1cs8A	GLN 19; ;HIS 163;ASN 187		OCS 25(Sulfonic Cys)
1icfA	GLN 19;CYS 25;HIS 163			CYS 25
1icfB	ASN 187
1icfC	GLN 19;CYS 25;HIS 163			CYS 25
1icfD	ASN 187
1mhwA	GLN 19; ;HIS 163		CSW 25(Oxidized Cys)
1mhwB	GLN 19; ;HIS 163		CSW 25(Oxidized Cys)
1mhwC	ASN 187
1mhwD	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]).

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