An Unusual Member of the Papain Superfamily: Mapping the Catalytic Cleft of the Marasmius Oreades Agglutinin (MOA) with a Caspase Inhibitor

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2016 Feb 23

PMID 26901797

Citations 4

Authors

Gabriele Cordara

Andre van Eerde

Elin M Grahn

Harry C Winter

Irwin J Goldstein

Ute Krengel

Affiliations

Soon will be listed here.

Abstract

Papain-like cysteine proteases (PLCPs) constitute the largest group of thiol-based protein degrading enzymes and are characterized by a highly conserved fold. They are found in bacteria, viruses, plants and animals and involved in a number of physiological and pathological processes, parasitic infections and host defense, making them interesting targets for drug design. The Marasmius oreades agglutinin (MOA) is a blood group B-specific fungal chimerolectin with calcium-dependent proteolytic activity. The proteolytic domain of MOA presents a unique structural arrangement, yet mimicking the main structural elements in known PLCPs. Here we present the X-ray crystal structure of MOA in complex with Z-VAD-fmk, an irreversible caspase inhibitor known to cross-react with PLCPs. The structural data allow modeling of the substrate binding geometry and mapping of the fundamental enzyme-substrate interactions. The new information consolidates MOA as a new, yet strongly atypical member of the papain superfamily. The reported complex is the first published structure of a PLCP in complex with the well characterized caspase inhibitor Z-VAD-fmk.

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References

Thornberry N, Bull H, Calaycay J, Chapman K, Howard A, Kostura M . A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes. Nature. 1992; 356(6372):768-74. DOI: 10.1038/356768a0. View

Taylor M, Baker K, Connerton I, Cummings N, Harris G, Henderson I . An unequivocal example of cysteine proteinase activity affected by multiple electrostatic interactions. Protein Eng. 1994; 7(10):1267-76. DOI: 10.1093/protein/7.10.1267. View

Wolfenden R, Snider M . The depth of chemical time and the power of enzymes as catalysts. Acc Chem Res. 2001; 34(12):938-45. DOI: 10.1021/ar000058i. View

Fearnhead H, Dinsdale D, Cohen G . An interleukin-1 beta-converting enzyme-like protease is a common mediator of apoptosis in thymocytes. FEBS Lett. 1995; 375(3):283-8. DOI: 10.1016/0014-5793(95)01228-7. View

Garcia-Calvo M, Peterson E, Leiting B, Ruel R, Nicholson D, Thornberry N . Inhibition of human caspases by peptide-based and macromolecular inhibitors. J Biol Chem. 1998; 273(49):32608-13. DOI: 10.1074/jbc.273.49.32608. View

Adams P, Afonine P, Bunkoczi G, Chen V, Davis I, Echols N . PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr D Biol Crystallogr. 2010; 66(Pt 2):213-21. PMC: 2815670. DOI: 10.1107/S0907444909052925. View

Kabsch W . XDS. Acta Crystallogr D Biol Crystallogr. 2010; 66(Pt 2):125-32. PMC: 2815665. DOI: 10.1107/S0907444909047337. View

Colaert N, Helsens K, Martens L, Vandekerckhove J, Gevaert K . Improved visualization of protein consensus sequences by iceLogo. Nat Methods. 2009; 6(11):786-7. DOI: 10.1038/nmeth1109-786. View

Menard R, Carriere J, Laflamme P, Plouffe C, Khouri H, Vernet T . Contribution of the glutamine 19 side chain to transition-state stabilization in the oxyanion hole of papain. Biochemistry. 1991; 30(37):8924-8. DOI: 10.1021/bi00101a002. View

10.

Khouri H, Vernet T, Menard R, Parlati F, Laflamme P, Tessier D . Engineering of papain: selective alteration of substrate specificity by site-directed mutagenesis. Biochemistry. 1991; 30(37):8929-36. DOI: 10.1021/bi00101a003. View

11.

Kruger R, Winter H, Stuckey J, Goldstein I, Dixon J . Cloning, expression, and characterization of the Galalpha 1,3Gal high affinity lectin from the mushroom Marasmius oreades. J Biol Chem. 2002; 277(17):15002-5. DOI: 10.1074/jbc.M200165200. View

12.

Lecaille F, Kaleta J, Bromme D . Human and parasitic papain-like cysteine proteases: their role in physiology and pathology and recent developments in inhibitor design. Chem Rev. 2002; 102(12):4459-88. DOI: 10.1021/cr0101656. View

13.

Krissinel E, Henrick K . Secondary-structure matching (SSM), a new tool for fast protein structure alignment in three dimensions. Acta Crystallogr D Biol Crystallogr. 2004; 60(Pt 12 Pt 1):2256-68. DOI: 10.1107/S0907444904026460. View

14.

Cordara G, Egge-Jacobsen W, Johansen H, Winter H, Goldstein I, Sandvig K . Marasmius oreades agglutinin (MOA) is a chimerolectin with proteolytic activity. Biochem Biophys Res Commun. 2011; 408(3):405-10. DOI: 10.1016/j.bbrc.2011.04.031. View

15.

Heinemann U, Pal G, Hilgenfeld R, Saenger W . Crystal and molecular structure of the sulfhydryl protease calotropin DI at 3.2 A resolution. J Mol Biol. 1982; 161(4):591-606. DOI: 10.1016/0022-2836(82)90410-7. View

16.

Winn M, Ballard C, Cowtan K, Dodson E, Emsley P, Evans P . Overview of the CCP4 suite and current developments. Acta Crystallogr D Biol Crystallogr. 2011; 67(Pt 4):235-42. PMC: 3069738. DOI: 10.1107/S0907444910045749. View

17.

Murshudov G, Skubak P, Lebedev A, Pannu N, Steiner R, Nicholls R . REFMAC5 for the refinement of macromolecular crystal structures. Acta Crystallogr D Biol Crystallogr. 2011; 67(Pt 4):355-67. PMC: 3069751. DOI: 10.1107/S0907444911001314. View

18.

Evans P . Scaling and assessment of data quality. Acta Crystallogr D Biol Crystallogr. 2005; 62(Pt 1):72-82. DOI: 10.1107/S0907444905036693. View

19.

Menard R, Carmona E, Plouffe C, Bromme D, Konishi Y, Lefebvre J . The specificity of the S1' subsite of cysteine proteases. FEBS Lett. 1993; 328(1-2):107-10. DOI: 10.1016/0014-5793(93)80975-z. View

20.

Bromme D . Papain-like cysteine proteases. Curr Protoc Protein Sci. 2008; Chapter 21:Unit 21.2. DOI: 10.1002/0471140864.ps2102s21. View