Taxonomic group: fungi / Basidiomycota
(Phylum: Basidiomycota)
Associated disease: infection due to Cryptococcus neoformans [ICD11:
XN3EH 
]
The structure was elucidated in this paperNCBI PubMed ID: 27872188Publication DOI: 10.1074/jbc.M116.767582Journal NLM ID: 2985121RPublisher: Baltimore, MD: American Society for Biochemistry and Molecular Biology
Correspondence: acasade1
jhu.edu
Institutions: Centre for Synthesis and Chemical Biology, UCD School of Chemistry and Chemical Biology, University College Dublin, Dublin, Ireland, Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY, USA, Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA
Studies in the 1980s first showed that some natural antibodies were "catalytic" and able to hydrolyze peptide or phosphodiester bonds in antigens. Many naturally occurring catalytic antibodies have since been isolated from human sera and associated with positive and negative outcomes in autoimmune disease and infection. The function and prevalence of these antibodies, however, remain unclear. A previous study suggested that the 18B7 monoclonal antibody against glucuronoxylomannan (GXM), the major component of the Cryptococcus neoformans polysaccharide capsule, hydrolyzed a peptide antigen mimetic. Using mass spectrometry and Förster resonance energy transfer techniques, we confirm and characterize the hydrolytic activity of 18B7 against peptide mimetics and show that 18B7 is able to hydrolyze an oligosaccharide substrate, providing the first example of a naturally occurring catalytic antibody for polysaccharides. Additionally, we show that the catalytic 18B7 antibody increases release of capsular polysaccharide from fungal cells. A serine protease inhibitor blocked peptide and oligosaccharide hydrolysis by 18B7, and a putative serine protease-like active site was identified in the light chain variable region of the antibody. An algorithm was developed to detect similar sites present in unique antibody structures in the Protein Data Bank. The putative site was found in 14 of 63 (22.2%) catalytic antibody structures and 119 of 1602 (7.4%) antibodies with no annotation of catalytic activity. The ability of many antibodies to cleave antigen, albeit slowly, supports the notion that this activity is an important immunoglobulin function in host defense. The discovery of GXM hydrolytic activity suggests new therapeutic possibilities for polysaccharide-binding antibodies.
antibody, monoclonal antibody, Computational Biology, enzyme kinetics, Cryptococcus neoformans, catalytic antibody, protein motif, serine protease, structural motif
Structure type: oligomer ; 1277.68
Location inside paper: Fig. 4A, GXM M2 motif
Compound class: glucuronoxylomannan
Contained glycoepitopes: IEDB_114701,IEDB_115136,IEDB_115576,IEDB_120354,IEDB_130701,IEDB_140116,IEDB_140630,IEDB_1406409,IEDB_144983,IEDB_145668,IEDB_151534,IEDB_152206,IEDB_164174,IEDB_167188,IEDB_174332,IEDB_2270799,IEDB_423153,IEDB_76933,IEDB_983930,SB_197,SB_44,SB_67,SB_72
Methods: MALDI-TOF MS
Biological activity: M2 mAb was able to hydrolyze short FLAG peptide
Comments, role: synthetic heptasaccharide with M2 motif, which is a major structural component of GXM in serotype A C. neoformans
NCBI Taxonomy refs (TaxIDs): 235443
Show glycosyltransferases
There is only one chemically distinct structure:
Found 
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(later renamed to: Cryptococcus neoformans var. grubii H99; Cryptococcus neoformans H99)