EzCatDB: M00029

DB codeM00029
RLCP classification1.13.11400.460
CATH domainDomain 13.10.170.20Catalytic domain
Domain 23.90.132.10Catalytic domain
Domain 32.10.55.10
Domain 42.30.34.10
E.C.3.4.24.36
CSA1lml


Enzyme Name
Swiss-protKEGG

P08148
Protein nameLeishmanolysinleishmanolysin
promastigote surface endopeptidase
glycoprotein gp63
Leishmania metalloproteinase
surface acid proteinase
promastigote surface protease
SynonymsEC 3.4.24.36
Cell surface protease
Major surface glycoprotein
Protein gp63
Promastigote surface endopeptidase
Major surface protease


Swiss-prot:Accession NumberP08148
Entry nameGP63_LEIMA
ActivityPreference 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-.
Subunit
Subcellular locationCell membrane, Lipid-anchor, GPI-anchor.
CofactorBinds 1 zinc ion per subunit.


CofactorsSubstratesProducts
KEGG-idC00038C00017C00012C00001C00017C00012
CompoundZincProteinPeptideH2OProteinPeptide
Typeheavy metalpeptide/proteinpeptide/proteinH2Opeptide/proteinpeptide/protein
1lmlA01Bound:_ZNUnboundUnbound
UnboundUnbound
1lmlA02UnboundUnboundUnbound
UnboundUnbound
1lmlA03UnboundUnboundUnbound
UnboundUnbound
1lmlA04UnboundUnboundUnbound
UnboundUnbound

Active-site residues
resource
PDB;1lml & Swiss-prot;P08148 & literature [4], [8], [11]
pdbCatalytic residuesCofactor-binding residues
1lmlA01GLU 265
HIS 264;HIS 268(Zinc binding)
1lmlA02
HIS 334(Zinc binding)
1lmlA03

1lmlA04


References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[11]p.1037-1040
[16]Fig.1, p.158

references
[1]
CommentsGPI-ANCHOR.
Medline ID91009116
PubMed ID2145267
JournalJ Biol Chem
Year1990
Volume265
Pages16955-64
AuthorsSchneider P, Ferguson MA, McConville MJ, Mehlert A, Homans SW, Bordier C
TitleStructure of the glycosyl-phosphatidylinositol membrane anchor of the Leishmania major promastigote surface protease.
Related Swiss-protP08148
[2]
PubMed ID8314766
JournalJ Biol Chem
Year1993
Volume268
Pages13994-4002
AuthorsWebb JR, McMaster WR
TitleMolecular cloning and expression of a Leishmania major gene encoding a single-stranded DNA-binding protein containing nine "CCHC" zinc finger motifs.
[3]
PubMed ID8084652
JournalParasitology
Year1994
Volume108 Suppl
PagesS29-36
AuthorsMcMaster WR, Morrison CJ, MacDonald MH, Joshi PB
TitleMutational and functional analysis of the Leishmania surface metalloproteinase GP63: similarities to matrix metalloproteinases.
[4]
PubMed ID8519803
JournalBiochim Biophys Acta
Year1995
Volume1253
Pages199-207
AuthorsMacdonald MH, Morrison CJ, McMaster WR
TitleAnalysis of the active site and activation mechanism of the Leishmania surface metalloproteinase GP63.
[5]
CommentsX-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS), DISULFIDE BONDS, AND CARBOHYDRATE-LINKAGE SITES ASN-300; ASN-407 AND ASN-534.
Medline ID95406217
PubMed ID7675788
JournalProteins
Year1995
Volume22
Pages58-66
AuthorsSchlagenhauf E, Etges R, Metcalf P
TitleCrystallization and preliminary X-ray diffraction studies of leishmanolysin, the major surface metalloproteinase from Leishmania major.
Related Swiss-protP08148
[6]
PubMed ID8573078
JournalBiochem J
Year1996
Volume313
Pages455-66
AuthorsSoteriadou KP, Tzinia AK, Panou-Pamonis E, Tsikaris V, Sakarellos-Daitsiotis M, Sakarellos C, Papapoulou Y, Matsas R
TitleAntigenicity and conformational analysis of the Zn(2+)-binding sites of two Zn(2+)-metalloproteases: Leishmania gp63 and mammalian endopeptidase-24.11.
[7]
PubMed ID11848831
JournalChem Rev
Year1996
Volume96
Pages2375-2434
AuthorsLipscomb WN, Strater N
TitleRecent Advances in Zinc Enzymology.
[8]
CommentsMUTAGENESIS OF TYR-254; HIS-264; GLU-265; HIS-268; ASN-300; ASN-407; ASN-534 AND ASN-577.
PubMed ID8626468
JournalJ Biol Chem
Year1996
Volume271
Pages7903-9
AuthorsMcGwire BS, Chang KP
TitlePosttranslational 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 Swiss-protP08148
[9]
PubMed ID9000250
JournalPept Res
Year1996
Volume9
Pages240-7
AuthorsTsikaris V, Sakarellos C, Sakarellos-Daitsiotis M, Cung MT, Marraud M, Konidou G, Tzinia A, Soteriadou KP
TitleUse of sequential oligopeptide carriers (SOCn) in the design of potent Leishmania gp63 immunogenic peptides.
[10]
CommentsCARBOHYDRATE-LINKAGE SITES ASN-307 AND ASN-400.
PubMed ID9041519
JournalMol Biochem Parasitol
Year1997
Volume84
Pages33-48
AuthorsFunk VA, Thomas-Oates JE, Kielland SL, Bates PA, Olafson RW
TitleA unique, terminally glucosylated oligosaccharide is a common feature on Leishmania cell surfaces.
Related Swiss-protP08148
[11]
CommentsX-RAY CRYSTALLOGRAPHY (1.86 ANGSTROMS).
Medline ID98416698
PubMed ID9739094
JournalStructure
Year1998
Volume6
Pages1035-46
AuthorsSchlagenhauf E, Etges R, Metcalf P
TitleThe crystal structure of the Leishmania major surface proteinase leishmanolysin (gp63).
Related PDB1lml
Related Swiss-protP08148
[12]
PubMed ID10464034
JournalExp Parasitol
Year1999
Volume93
Pages7-22
AuthorsPuentes F, Guzman F, Marin V, Alonso C, Patarroyo ME, Moreno A
TitleLeishmania: fine mapping of the Leishmanolysin molecule's conserved core domains involved in binding and internalization.
[13]
PubMed ID10924466
JournalGenetics
Year2000
Volume155
Pages1683-92
AuthorsAlvarez-Valin F, Tort JF, Bernardi G
TitleNonrandom spatial distribution of synonymous substitutions in the GP63 gene from Leishmania.
[14]
PubMed ID12137567
JournalBiochem J
Year2002
Volume367
Pages761-9
AuthorsCorradin S, Ransijn A, Corradin G, Bouvier J, Delgado MB, Fernandez-Carneado J, Mottram JC, Vergeres G, Mauel J
TitleNovel peptide inhibitors of Leishmania gp63 based on the cleavage site of MARCKS (myristoylated alanine-rich C kinase substrate)-related protein.
[15]
PubMed ID14563532
JournalMol Biochem Parasitol
Year2003
Volume132
Pages1-16
AuthorsYao C, Donelson JE, Wilson ME
TitleThe major surface protease (MSP or GP63) of Leishmania sp. Biosynthesis, regulation of expression, and function.
[16]
PubMed ID12746556
JournalMol Biotechnol
Year2003
Volume24
Pages157-202
AuthorsGomis-Ruth FX
TitleStructural aspects of the metzincin clan of metalloendopeptidases.

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.

createdupdated
2005-10-202009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2010)
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)

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