PDBsum entry 6n3s

Hydrolase

PDB id: 6n3s

Contents

Protein chains

215 a.a.

Ligands

EDO ×5

PO4 ×2

Waters ×514

PDB id:

6n3s

Name:

Hydrolase

Title:

Crystal structure of apo-cruzain

Structure:

Cruzipain. Chain: a, b. Synonym: cruzaine,major cysteine proteinase. Engineered: yes. Mutation: yes

Source:

Trypanosoma cruzi. Organism_taxid: 5693. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.19Å R-factor: 0.139 R-free: 0.165

Authors:

E.B.Silva,E.Dall,F.T.G.Rodrigues,R.S.Ferreira,H.Brandstetter

Key ref:

E.Barbosa da Silva et al. (2019). Cruzain structures: apocruzain and cruzain bound to S-methyl thiomethanesulfonate and implications for drug design. Acta Crystallogr F Struct Biol Commun, 75, 419-427. PubMed id: 31204688 DOI: 10.1107/S2053230X19006320

Date:

16-Nov-18 Release date: 29-May-19

Protein chains

P25779  (CYSP_TRYCR) -  Cruzipain from Trypanosoma cruzi

Seq: 467 a.a.

Struc: 215 a.a.

Enzyme reactions

• Enzyme class: E.C.3.4.22.51 - cruzipain.

DOI no: 10.1107/S2053230X19006320

Acta Crystallogr F Struct Biol Commun 75:419-427 (2019)

PubMed id: 31204688

Cruzain structures: apocruzain and cruzain bound to S-methyl thiomethanesulfonate and implications for drug design.

E.Barbosa da Silva, E.Dall, P.Briza, H.Brandstetter, R.S.Ferreira.

ABSTRACT

Chagas disease, which is caused by Trypanosoma cruzi, affects more than six million people worldwide. Cruzain is the major cysteine protease involved in the survival of this parasite. Here, the expression, purification and crystallization of this enzyme are reported. The cruzain crystals diffracted to 1.2 Å resolution, yielding two novel cruzain structures: apocruzain and cruzain bound to the reversible covalent inhibitor S-methyl thiomethanesulfonate. Mass-spectrometric experiments confirmed the presence of a methylthiol group attached to the catalytic cysteine. Comparison of these structures with previously published structures indicates the rigidity of the cruzain structure. These results provide further structural information about the enzyme and may help in new in silico studies to identify or optimize novel prototypes of cruzain inhibitors.