Found 3 structures.
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1. Compound ID: 17598
b-D-Xylp-(1-2)-+
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b-D-Xylp-(1-2)-+ |
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b-D-GlcpA-(1-2)-a-D-Manp6Ac-(1-3)-a-D-Manp-(1-3)-a-D-Manp-(1-3)-a-D-Manp-(1--/O-spacer, human serum albumin/ |
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Structure type: oligomer
Aglycon: O-spacer, human serum albumin
Trivial name: glucuronoxylomannan (GXM)
Compound class: CPS
Contained glycoepitopes: IEDB_114701,IEDB_115136,IEDB_115576,IEDB_130701,IEDB_140116,IEDB_140630,IEDB_144983,IEDB_145668,IEDB_151534,IEDB_152206,IEDB_164174,IEDB_167188,IEDB_174332,IEDB_423153,IEDB_76933,IEDB_983930,SB_197,SB_44,SB_67,SB_72
The structure is contained in the following publication(s):
- Article ID: 6892
Nakouzi A, Zhang T, Oscarson S, Casadevall A "The common Cryptococcus neoformans glucuronoxylomannan M2 motif elicits non-protective antibodies" -
Vaccine 27(27) (2009) 3513-3518
The Cryptococcus neoformans capsular glucuronoxylomannan (GXM) is a potential vaccine antigen that can elicit protective and non-protective antibodies. In an attempt to focus the immune response on a single antigenic component, a heptasaccharide oligosaccharide representing the major structural motif (M2) of the most common clinical isolate was synthesized and conjugated to human serum albumin (HSA). Monoclonal antibodies (mAbs) generated from mice immunized with M2–HSA produced the characteristic punctuate immunofluorescence associated with non-protective mAbs. None of the mAbs elicited by M2 immunization was opsonic. Passive administration of mAbs elicited by M2–HSA was not protective and there was no difference in the survival of mice immunized with M2–HSA and HSA. Hence, we conclude that the M2 motif represents an antigenic determinant in C. neoformans GXM that elicits non-protective responses and is not a suitable vaccine candidate. Furthermore, the results illustrate the first molecular assignment of a C. neoformans polysaccharide epitope and suggest a general strategy for the identification of GXM epitopes.
antibody, vaccine, immune response, Cryptococcus neoformans
NCBI PubMed ID: 19464529Publication DOI: 10.1016/j.vaccine.2009.03.089Journal NLM ID: 8406899Publisher: Elsevier
Correspondence: casadeva@aecom.yu.edu (A. Casadevall)
Institutions: Centre for Synthesis and Chemical Biology, UCD School of Chemistry and Chemical Biology, University College Dublin, Belfield, Dublin 4, Ireland, Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, Department of Medicine (Division of Infectious Diseases), Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461
Methods: DNA sequencing, ELISA, serological methods, statistical analysis, immunization, phagocytosis assay, immunofluorescence analysis
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2. Compound ID: 18420
b-D-Xylp-(1-2)-+
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b-D-GlcpA-(1-2)-+ b-D-Xylp-(1-2)-+ |
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-3)-a-D-Manp6Ac-(1-3)-a-D-Manp-(1-3)-a-D-Manp6Ac-(1- |
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Structure type: structural motif or average structure
Compound class: O-polysaccharide, glucuronoxylomannan
Contained glycoepitopes: IEDB_114701,IEDB_115136,IEDB_115576,IEDB_130701,IEDB_140116,IEDB_140630,IEDB_1406409,IEDB_1406410,IEDB_144983,IEDB_145668,IEDB_151534,IEDB_152206,IEDB_164174,IEDB_167188,IEDB_174332,IEDB_423153,IEDB_76933,IEDB_983930,SB_197,SB_44,SB_67,SB_72
The structure is contained in the following publication(s):
- Article ID: 7243
Cherniak R, Sundstrom JB "Polysaccharide antigens of the capsule of Cryptococcus neoformans" -
Infection and Immunity 62(5) (1994) 1507-1512
The major significance of the capsular polysaccharide of C. neoformans is its role in potentiating opportunistic infections by the yeast. It has the ability to exert a broad spectrum of influences on the immune response, from activation of phagocytic cells and complement components of the alternative pathway, to the induction of specific antibody, T-suppressor cells, DTH responses, and cytokines (51). These biological properties along with the serotype specificities are all determined by the physical properties and chemical structures of the polysaccharide antigens that compose the capsule. There is evidence not only for an association of lethal infections with serotype A in patients with advanced AIDS (34, 56), but also for a role for the capsule in directly influencing the infection of CD4 + cells by HIV (57). Together, these phenomena raise intriguing questions about the possible connection between the chemistry of these capsular antigens and cryptococcal infections in AIDS patients. One speculation is that AIDS creates the optimal physiological conditions for the establishment and spread of cryptococcosis. It has been observed that during the progression of AIDS there is a shift towards a T-2 response (14). This could lead to conditions that would inhibit the cellular immune responses that block dissemination of cryptococcal infections. Thus, an important consideration in the application of vaccine or immune modulation therapies in the treatment of cryptococcosis in AIDS victims would be the design of vaccines that could boost the T-1 immune response. It has been shown that the form and dose of an antigenic challenge can influence the induction of a T-1 or T-2 immune response (61). Recently, Murphy has reported that gamma interferon and interleukin 2 are up-regulated in the spleens of mice that produce anticryptococcal T(DH) and T(AMP) cells in response to immunogenic doses of cryptococcal culture filtrate antigen given with Freund's complete adjuvant (49). Perhaps purified cryptococcal antigens (e.g., MP) conjugated to an appropriate carrier or adjuvant could be used in therapeutic strategies to limit cryptococcosis in immunocompromised individuals. Future investigations of virulence and pathogenicity in the context of defined polysaccharide antigens from encapsulated strains of C. neoformans will contribute to a better understanding of the regulation of cryptococcal infection and immunity at the cellular and molecular levels. This information could lead to (i) the development of effective vaccines, designed to induce not only a sufficient but also an appropriate immune response to cryptococcal antigens, and (ii) a better understanding of how these polysaccharide antigens influence T-1 and T-2 T-cell responses, how they potentiate opportunistic cryptococcosis in HIV-infected individuals, and how virulence and serotypes are related to the molecular structures of these antigens.
antigen, capsular polysaccharide, Cryptococcus neoformans, cryptococcosis
NCBI PubMed ID: 8168912Journal NLM ID: 0246127Publisher: American Society for Microbiology
Correspondence: Cherniak R
Institutions: Department of Chemistry, Georgia State University, University Plaza, Atlanta, USA, Department of Pathology and Laboratory Medicine, Emory University, Atlanta, USA
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3. Compound ID: 18939
b-D-Xylp-(1-2)-+
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b-D-Xylp-(1-2)-+ |
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b-D-GlcpA-(1-2)-a-D-Manp6Ac-(1-3)-a-D-Manp-(1-3)-a-D-Manp6Ac-(1-3)-a-D-Manp-(1-1)-EtN |
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Structure type: oligomer
; 1277.68
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_423153,IEDB_76933,IEDB_983930,SB_197,SB_44,SB_67,SB_72
The structure is contained in the following publication(s):
- Article ID: 7474
Bowen A, Wear MP, Cordero RJ, Oscarson S, Casadevall A "A monoclonal antibody to Cryptococcus neoformans glucuronoxylomannan manifests hydrolytic activity for both peptides and polysaccharides" -
Journal of Biological Chemistry 292(2) (2017) 417-434
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
NCBI 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: 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, Centre for Synthesis and Chemical Biology, UCD School of Chemistry and Chemical Biology, University College Dublin, Dublin, Ireland
Methods: MALDI-TOF MS
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