PDBsum entry 1lml

Leishmanolysin

PDB id: 1lml

Contents

Protein chain

465 a.a. *

Metals

_ZN

Waters ×212

* Residue conservation analysis

PDB id:

1lml

Name:

Leishmanolysin

Title:

Leishmanolysin

Structure:

Leishmanolysin. Chain: a. Synonym: gp63 protein, psp. Ec: 3.4.24.36

Source:

Leishmania major. Organism_taxid: 5664. Strain: lrc-l119. Cellular_location: membrane bound

Resolution:

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

Date:

13-Mar-97 Release date: 17-Sep-97

Protein chain

P08148  (GP63_LEIMA) -  Leishmanolysin from Leishmania major

Seq: 602 a.a.

Struc: 465 a.a.

Enzyme reactions

• Enzyme class: E.C.3.4.24.36 - leishmanolysin.
• 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+)

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.

ABSTRACT

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.