PDBsum entry 1lml

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protein metals links
Leishmanolysin PDB id
Protein chain
465 a.a. *
Waters ×212
* Residue conservation analysis
PDB id:
Name: Leishmanolysin
Title: Leishmanolysin
Structure: Leishmanolysin. Chain: a. Synonym: gp63 protein, psp. Ec:
Source: Leishmania major. Organism_taxid: 5664. Strain: lrc-l119. Cellular_location: membrane bound
1.86Å     R-factor:   0.191     R-free:   0.208
Authors: E.Schlagenhauf,R.Etges,P.Metcalf
Key ref:
E.Schlagenhauf et al. (1998). The crystal structure of the Leishmania major surface proteinase leishmanolysin (gp63). Structure, 6, 1035-1046. PubMed id: 9739094 DOI: 10.1016/S0969-2126(98)00104-X
13-Mar-97     Release date:   17-Sep-97    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P08148  (GP63_LEIMA) -  Leishmanolysin
602 a.a.
465 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Leishmanolysin.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 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-.
      Cofactor: Ca(2+); Zn(2+)
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   1 term 
  Biological process     cell adhesion   2 terms 
  Biochemical function     metalloendopeptidase activity     1 term  


DOI no: 10.1016/S0969-2126(98)00104-X Structure 6:1035-1046 (1998)
PubMed id: 9739094  
The crystal structure of the Leishmania major surface proteinase leishmanolysin (gp63).
E.Schlagenhauf, R.Etges, P.Metcalf.
BACKGROUND: Despite their medical importance, there is little available structural information for the surface antigens of infectious protozoa. Diseases caused by the protozoan parasite Leishmania are common in many developing countries. Human infection occurs during the bite of infected sandfilies, when Leishmania promastigote cells from the insect gut enter the bloodstream. Promastigotes in the blood parasitize macrophages, often causing serious disease. Leishmanolysin is the predominant protein surface antigen of promastigotes, and is assumed to have a key role during infection. Leishmanolysin is a membrane-bound zinc proteinase, active in situ. Similar molecules exist in other trypanomastid protozoa. RESULTS: Two crystal forms of leishmanolysin were obtained from protein purified from promastigote membranes. A single lead derivative in both crystal forms was used to solve the structure. The structure reveals three domains, two of which have novel folds. The N-terminal domain has a similar structure to the catalytic modules of zinc proteinases. The structure clearly shows that leishmanolysin is a member of the metzincin class of zinc proteinases. CONCLUSIONS: The unexpected metzincin features of the leishmanolysin structure suggest that the metzincin fold may be more widespread than indicated by sequence homologies amongst existing metzincin zinc proteinases. The similarity of the active-site structure to previously well characterized metzincin class zinc proteinases should aid the development of specific inhibitors. These inhibitors might be used to determine the function of leishmanolysin in the insect and during mammalian infection, and may aid the development of drugs for human leishmaniasis.
  Selected figure(s)  
Figure 1.
Figure 1. Leishmanolysin domain structure and surface representation. (a) Ribbon representation of the structure with the N-terminal domain shown in red, the central domain in green, and the C-terminal domain in blue. Disulfide bonds are shown in yellow and the active site zinc atom is represented as a magenta sphere. The molecule is viewed looking into the active-site cleft. (b) Surface representation of the molecule with regions of negative potential shown in red and positive regions in blue.
  The above figure is reprinted by permission from Cell Press: Structure (1998, 6, 1035-1046) copyright 1998.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19858295 C.Yao (2010).
Major surface protease of trypanosomatids: one size fits all?
  Infect Immun, 78, 22-31.  
20145707 V.Marcoux, G.Wei, H.Tabel, and H.J.Bull (2010).
Characterization of major surface protease homologues of Trypanosoma congolense.
  J Biomed Biotechnol, 2010, 418157.  
19604476 E.E.Chufán, M.De, B.A.Eipper, R.E.Mains, and L.M.Amzel (2009).
Amidation of bioactive peptides: the structure of the lyase domain of the amidating enzyme.
  Structure, 17, 965-973.
PDB codes: 3fvz 3fw0
19201757 F.X.Gomis-Rüth (2009).
Catalytic domain architecture of metzincin metalloproteases.
  J Biol Chem, 284, 15353-15357.  
19706689 N.Cobbe, K.M.Marshall, S.Gururaja Rao, C.W.Chang, F.Di Cara, E.Duca, S.Vass, A.Kassan, and M.M.Heck (2009).
The conserved metalloprotease invadolysin localizes to the surface of lipid droplets.
  J Cell Sci, 122, 3414-3423.  
  19238247 A.Razzazan, M.R.Saberi, and M.R.Jaafari (2008).
Insights from the analysis of a predicted model of gp63 in Leishmania donovani.
  Bioinformation, 3, 114-118.  
17953481 P.M.Grandgenett, K.Otsu, H.R.Wilson, M.E.Wilson, and J.E.Donelson (2007).
A function for a specific zinc metalloprotease of African trypanosomes.
  PLoS Pathog, 3, 1432-1445.  
16708363 G.Bianchini, A.Bocedi, P.Ascenzi, E.Gavuzzo, F.Mazza, and M.Aschi (2006).
Molecular dynamics simulation of Leishmania major surface metalloprotease GP63 (leishmanolysin).
  Proteins, 64, 385-390.  
16145937 K.Victoir, J.Arevalo, S.De Doncker, D.C.Barker, T.Laurent, E.Godfroid, A.Bollen, D.Le Ray, and J.C.Dujardin (2005).
Complexity of the major surface protease (msp) gene organization in Leishmania (Viannia) braziliensis: evolutionary and functional implications.
  Parasitology, 131, 207-214.  
15557119 B.McHugh, S.A.Krause, B.Yu, A.M.Deans, S.Heasman, P.McLaughlin, and M.M.Heck (2004).
Invadolysin: a novel, conserved metalloprotease links mitotic structural rearrangements with cell migration.
  J Cell Biol, 167, 673-686.  
12716904 A.E.Gruszynski, A.DeMaster, N.M.Hooper, and J.D.Bangs (2003).
Surface coat remodeling during differentiation of Trypanosoma brucei.
  J Biol Chem, 278, 24665-24672.  
12707278 D.J.LaCount, A.E.Gruszynski, P.M.Grandgenett, J.D.Bangs, and J.E.Donelson (2003).
Expression and function of the Trypanosoma brucei major surface protease (GP63) genes.
  J Biol Chem, 278, 24658-24664.  
11882664 I.Pelletier, and S.Sato (2002).
Specific recognition and cleavage of galectin-3 by Leishmania major through species-specific polygalactose epitope.
  J Biol Chem, 277, 17663-17670.  
12045098 M.Klemba, and D.E.Goldberg (2002).
Biological roles of proteases in parasitic protozoa.
  Annu Rev Biochem, 71, 275-305.  
  10924466 F.Alvarez-Valin, J.F.Tort, and G.Bernardi (2000).
Nonrandom spatial distribution of synonymous substitutions in the GP63 gene from Leishmania.
  Genetics, 155, 1683-1692.  
10464270 S.Corradin, A.Ransijn, G.Corradin, M.A.Roggero, A.A.Schmitz, P.Schneider, J.Mauël, and G.Vergères (1999).
MARCKS-related protein (MRP) is a substrate for the Leishmania major surface protease leishmanolysin (gp63).
  J Biol Chem, 274, 25411-25418.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.