DB code: M00029

RLCP classification 1.13.11400.460 : Hydrolysis
CATH domain 3.10.170.20 : Elastase; domain 1 Catalytic domain
3.90.132.10 : Leishmanolysin; domain 2 Catalytic domain
2.10.55.10 : Leishmanolysin; domain 3
2.30.34.10 : Leishmanolysin; domain 4
E.C. 3.4.24.36
CSA 1lml
M-CSA 1lml
MACiE

CATH domain Related DB codes (homologues)

Uniprot Enzyme Name
UniprotKB Protein name Synonyms MEROPS Pfam
P08148 Leishmanolysin
EC 3.4.24.36
Cell surface protease
Major surface glycoprotein
Major surface protease
Promastigote surface endopeptidase
Protein gp63
M08.001 (Metallo)
PF01457 (Peptidase_M8)
[Graphical View]

KEGG enzyme name
leishmanolysin
promastigote surface endopeptidase
glycoprotein gp63
Leishmania metalloproteinase
surface acid proteinase
promastigote surface protease

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P08148 GP63_LEIMA Preference for hydrophobic residues at P1 and P1'' and basic residues at P2'' and P3''. A model nonapeptide is cleaved at -Ala-Tyr-|-Leu-Lys-Lys-. Cell membrane, Lipid-anchor, GPI-anchor. Binds 1 zinc ion per subunit.

KEGG Pathways
Map code Pathways E.C.

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00038 C00017 C00012 C00001 C00017 C00012
E.C.
Compound Zinc Protein Peptide H2O Protein Peptide
Type heavy metal peptide/protein peptide/protein H2O peptide/protein peptide/protein
ChEBI 29105
15377
PubChem 32051
22247451
962
1lmlA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Unbound
1lmlA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1lmlA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1lmlA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
PDB;1lml & Swiss-prot;P08148 & literature [4], [8], [11]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1lmlA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 265 HIS 264;HIS 268(Zinc binding)
1lmlA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 334(Zinc binding)
1lmlA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1lmlA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[11]
p.1037-1040
[16]
Fig.1, p.158

References
[1]
Resource
Comments GPI-ANCHOR.
Medline ID 91009116
PubMed ID 2145267
Journal J Biol Chem
Year 1990
Volume 265
Pages 16955-64
Authors Schneider P, Ferguson MA, McConville MJ, Mehlert A, Homans SW, Bordier C
Title Structure of the glycosyl-phosphatidylinositol membrane anchor of the Leishmania major promastigote surface protease.
Related PDB
Related UniProtKB P08148
[2]
Resource
Comments
Medline ID
PubMed ID 8314766
Journal J Biol Chem
Year 1993
Volume 268
Pages 13994-4002
Authors Webb JR, McMaster WR
Title Molecular cloning and expression of a Leishmania major gene encoding a single-stranded DNA-binding protein containing nine "CCHC" zinc finger motifs.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 8084652
Journal Parasitology
Year 1994
Volume 108 Suppl
Pages S29-36
Authors McMaster WR, Morrison CJ, MacDonald MH, Joshi PB
Title Mutational and functional analysis of the Leishmania surface metalloproteinase GP63: similarities to matrix metalloproteinases.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 8519803
Journal Biochim Biophys Acta
Year 1995
Volume 1253
Pages 199-207
Authors Macdonald MH, Morrison CJ, McMaster WR
Title Analysis of the active site and activation mechanism of the Leishmania surface metalloproteinase GP63.
Related PDB
Related UniProtKB
[5]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS), DISULFIDE BONDS, AND CARBOHYDRATE-LINKAGE SITES ASN-300; ASN-407 AND ASN-534.
Medline ID 95406217
PubMed ID 7675788
Journal Proteins
Year 1995
Volume 22
Pages 58-66
Authors Schlagenhauf E, Etges R, Metcalf P
Title Crystallization and preliminary X-ray diffraction studies of leishmanolysin, the major surface metalloproteinase from Leishmania major.
Related PDB
Related UniProtKB P08148
[6]
Resource
Comments
Medline ID
PubMed ID 8573078
Journal Biochem J
Year 1996
Volume 313
Pages 455-66
Authors Soteriadou KP, Tzinia AK, Panou-Pamonis E, Tsikaris V, Sakarellos-Daitsiotis M, Sakarellos C, Papapoulou Y, Matsas R
Title Antigenicity and conformational analysis of the Zn(2+)-binding sites of two Zn(2+)-metalloproteases: Leishmania gp63 and mammalian endopeptidase-24.11.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 11848831
Journal Chem Rev
Year 1996
Volume 96
Pages 2375-2434
Authors Lipscomb WN, Strater N
Title Recent Advances in Zinc Enzymology.
Related PDB
Related UniProtKB
[8]
Resource
Comments MUTAGENESIS OF TYR-254; HIS-264; GLU-265; HIS-268; ASN-300; ASN-407; ASN-534 AND ASN-577.
Medline ID
PubMed ID 8626468
Journal J Biol Chem
Year 1996
Volume 271
Pages 7903-9
Authors McGwire BS, Chang KP
Title Posttranslational regulation of a Leishmania HEXXH metalloprotease (gp63). The effects of site-specific mutagenesis of catalytic, zinc binding, N-glycosylation, and glycosyl phosphatidylinositol addition sites on N-terminal end cleavage, intracellular stability, and extracellular exit.
Related PDB
Related UniProtKB P08148
[9]
Resource
Comments
Medline ID
PubMed ID 9000250
Journal Pept Res
Year 1996
Volume 9
Pages 240-7
Authors Tsikaris V, Sakarellos C, Sakarellos-Daitsiotis M, Cung MT, Marraud M, Konidou G, Tzinia A, Soteriadou KP
Title Use of sequential oligopeptide carriers (SOCn) in the design of potent Leishmania gp63 immunogenic peptides.
Related PDB
Related UniProtKB
[10]
Resource
Comments CARBOHYDRATE-LINKAGE SITES ASN-307 AND ASN-400.
Medline ID
PubMed ID 9041519
Journal Mol Biochem Parasitol
Year 1997
Volume 84
Pages 33-48
Authors Funk VA, Thomas-Oates JE, Kielland SL, Bates PA, Olafson RW
Title A unique, terminally glucosylated oligosaccharide is a common feature on Leishmania cell surfaces.
Related PDB
Related UniProtKB P08148
[11]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.86 ANGSTROMS).
Medline ID 98416698
PubMed ID 9739094
Journal Structure
Year 1998
Volume 6
Pages 1035-46
Authors Schlagenhauf E, Etges R, Metcalf P
Title The crystal structure of the Leishmania major surface proteinase leishmanolysin (gp63).
Related PDB 1lml
Related UniProtKB P08148
[12]
Resource
Comments
Medline ID
PubMed ID 10464034
Journal Exp Parasitol
Year 1999
Volume 93
Pages 7-22
Authors Puentes F, Guzman F, Marin V, Alonso C, Patarroyo ME, Moreno A
Title Leishmania: fine mapping of the Leishmanolysin molecule's conserved core domains involved in binding and internalization.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 10924466
Journal Genetics
Year 2000
Volume 155
Pages 1683-92
Authors Alvarez-Valin F, Tort JF, Bernardi G
Title Nonrandom spatial distribution of synonymous substitutions in the GP63 gene from Leishmania.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 12137567
Journal Biochem J
Year 2002
Volume 367
Pages 761-9
Authors Corradin S, Ransijn A, Corradin G, Bouvier J, Delgado MB, Fernandez-Carneado J, Mottram JC, Vergeres G, Mauel J
Title Novel peptide inhibitors of Leishmania gp63 based on the cleavage site of MARCKS (myristoylated alanine-rich C kinase substrate)-related protein.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 14563532
Journal Mol Biochem Parasitol
Year 2003
Volume 132
Pages 1-16
Authors Yao C, Donelson JE, Wilson ME
Title The major surface protease (MSP or GP63) of Leishmania sp. Biosynthesis, regulation of expression, and function.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 12746556
Journal Mol Biotechnol
Year 2003
Volume 24
Pages 157-202
Authors Gomis-Ruth FX
Title Structural aspects of the metzincin clan of metalloendopeptidases.
Related PDB
Related UniProtKB

Comments
This enzyme belongs to the peptidase family-M8.
According to the literature [16], this enzyme is classified as a metzincin class zinc proteinase, which includes astacin (S00394 in EzCatDB), serralysin (D00236), adamalysin (S00399). However, the homologous family in the CATH classification of these enzymes (CATH 3.40.390.10) are different from that of this enzyme, although the strucutre of active site (residues 200-272) of this enzyme can be superimposed to those active sites. It suggests a distant evolutionarily relationships with these enzymes.
According to the literature [11] & [16], this enzyme seems to have a similar mechanism to those of the above enzymes. Among them, adamalysin (S00399) and neutrophil collagenase (S00397) have got similar active sites, suggesting that this enzyme has the same reaction mechanism as those of these enzymes.

Created Updated
2005-10-20 2009-02-26