PDBsum entry: 1ms3

Hydrolase

PDB-id: 1ms3

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Description

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Header records

References

PROCHECK

Protein chains

623 a.a. *

Waters ×1152

* Residue conservation analysis

Tools

Clefts Calculation

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PDB id:

1ms3

Name:

Hydrolase

Title:

Monoclinic form of trypanosoma cruzi trans-sialidase

Structure:

Trans-sialidase. Chain: a, b. Fragment: enzymatic globular core. Engineered: yes. Mutation: yes

Source:

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

UniProt:

Chains A, B: Q26966 (Q26966_TRYCR)

Seq:

Struc:

Seq:

Struc:

Seq:

642 a.a.

Struc:

623 a.a.*

Key:

Secondary structure

CATH domain

* PDB and UniProt seqs differ at 11 residue positions (black crosses)

Resolution:

1.65Å

R-factor:

0.164

R-free:

0.192

Authors:

A.Buschiazzo,M.F.Amaya,M.L.Cremona,A.C.Frasch,P.M.Alzari

Key ref:

A.Buschiazzo et al. (2002). The crystal structure and mode of action of trans-sialidase, a key enzyme in Trypanosoma cruzi pathogenesis.. Mol Cell, 10, 757-768. [PubMed id: 12419220] [DOI: 10.1016/S1097-2765(02)00680-9]

Date:

19-Sep-02

Release date:

25-Mar-03

Related entries:

1mr5
orthorhombic form of trypanosoma cruzi trans-sialidase
1ms0
monoclinic form of trypanosoma cruzi trans-sialidase, in
complex with 3-deoxy-2,3-dehydro-n-acetylneuraminic acid
(dana)and lactose
1ms1
monoclinic form of trypanosoma cruzi trans-sialidase, in
complex with 3-deoxy-2,3-dehydro-n-acetylneuraminic acid
(dana)
... plus others (see Header records)

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Clefts

Surface

Key reference

DOI no: 10.1016/S1097-2765(02)00680-9

Mol Cell 10:757-768 (2002)

PubMed id: 12419220

The crystal structure and mode of action of trans-sialidase, a key enzyme in Trypanosoma cruzi pathogenesis.

A.Buschiazzo, M.F.Amaya, M.L.Cremona, A.C.Frasch, P.M.Alzari.

ABSTRACT

Trans-sialidases (TS) are GPI-anchored surface enzymes expressed in specific developmental stages of trypanosome parasites like Trypanosoma cruzi, the etiologic agent of Chagas disease, and T. brucei, the causative agent of sleeping sickness. TS catalyzes the transfer of sialic acid residues from host to parasite glycoconjugates through a transglycosidase reaction that appears to be critical for T. cruzi survival and cell invasion capability. We report here the structure of the T. cruzi trans-sialidase, alone and in complex with sugar ligands. Sialic acid binding is shown to trigger a conformational switch that modulates the affinity for the acceptor substrate and concomitantly creates the conditions for efficient transglycosylation. The structure provides a framework for the structure-based design of novel inhibitors with potential therapeutic applications.

Selected figure(s)

Figure 4.
Figure 4. Lactose Binding to TcTS(A) Complete BIAcore sensorgrams showing the interaction between the inactive mutant Asp59Asn and sialic acid (continuous line). Lactose (10 mM) was injected after equilibrating the protein in the presence (continuous line) or absence (dashed line) of sialic acid.(b) Detailed view of the interaction between TcTS and lactose, demonstrating that the acceptor substrate only binds to TcTS when sialic acid is present.

Figure 5.
Figure 5. TcTS-Lactose Interactions(A) Electron density (2Fo-Fc) map, contoured at 1 σ, of the lactose binding site in the triclinic crystal form. The loop containing Gly145/Gly146 from a neighbor molecule in the crystal is also shown.(B) Electron density (2Fo-Fc) map, contoured at 1 σ, showing the lactose and DANA molecules in the ternary complex.(C) Schematic diagram showing protein-carbohydrate hydrogen bonding interactions.(D) Stacking interactions of the lactose moiety with the aromatic rings of Trp312 and Tyr119 in the ternary complex.

The above figures are reprinted by permission from Cell Press: Mol Cell (2002, 10, 757-768) copyright 2002.

Figures were selected by an automated process.