PDBsum entry 4xui

Hydrolase/hydrolase inhibitor

PDB id: 4xui

Contents

Protein chains

215 a.a.

Ligands

2VC ×3

EDO ×4

Waters ×81

PDB id:

4xui

Name:

Hydrolase/hydrolase inhibitor

Title:

Crystal structure analysis of cruzain bound to the no-covalent analog of wrr-483 (wrr-669)

Structure:

Cruzipain. Chain: a, b, c. Fragment: unp residues 122-337. Synonym: cruzaine,major cysteine proteinase. Engineered: yes

Source:

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

Resolution:

2.51Å R-factor: 0.163 R-free: 0.189

Authors:

A.Tochowicz,J.H.Mckerrow

Key ref:

B.D.Jones et al. (2016). Synthesis and Evaluation of Oxyguanidine Analogues of the Cysteine Protease Inhibitor WRR-483 against Cruzain. Acs Med Chem Lett, 7, 77-82. PubMed id: 26819670 DOI: 10.1021/acsmedchemlett.5b00336

Date:

26-Jan-15 Release date: 11-Mar-15

Supersedes:

4pi4

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: 10.1021/acsmedchemlett.5b00336

Acs Med Chem Lett 7:77-82 (2016)

PubMed id: 26819670

Synthesis and Evaluation of Oxyguanidine Analogues of the Cysteine Protease Inhibitor WRR-483 against Cruzain.

B.D.Jones, A.Tochowicz, Y.Tang, M.D.Cameron, L.I.McCall, K.Hirata, J.L.Siqueira-Neto, S.L.Reed, J.H.McKerrow, W.R.Roush.

ABSTRACT

A series of oxyguanidine analogues of the cysteine protease inhibitor WRR-483 were synthesized and evaluated against cruzain, the major cysteine protease of the protozoan parasite Trypanosoma cruzi. Kinetic analyses of these analogues indicated that they have comparable potency to previously prepared vinyl sulfone cruzain inhibitors. Co-crystal structures of the oxyguanidine analogues WRR-666 (4) and WRR-669 (7) bound to cruzain demonstrated different binding interactions with the cysteine protease, depending on the aryl moiety of the P1' inhibitor subunit. Specifically, these data demonstrate that WRR-669 is bound noncovalently in the crystal structure. This represents a rare example of noncovalent inhibition of a cysteine protease by a vinyl sulfone inhibitor.