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Mammalian allergens
Published in Richard F. Lockey, Dennis K. Ledford, Allergens and Allergen Immunotherapy, 2020
Tuomas Virtanen, Marja Rytkönen-Nissinen
Despite the low sequential identities between lipocalins, they share a common three-dimensional structure (Figure 16.3) [18]. The central β-barrel of lipocalins is composed of eight antiparallel β-strands, and it encloses an internal ligand-binding site (Figures 16.2 and 16.3). At the N-terminus, there is a 310 helix, whereas at the C-terminus, there is an α-helix of variable length. The oligomerization (arrangement in multisubunit complexes) of lipocalins is variable (Table 16.2). The three-dimensional structures of several lipocalin allergens are known (Table 16.2).
Peptide Structure and Analysis
Published in Marco Chinol, Giovanni Paganelli, Radionuclide Peptide Cancer Therapy, 2016
Carlo Pedone, Giancarlo Morelli, Diego Tesauro, Michele Saviano
In proteins it is well-known that α-helices and β-sheets (Fig. 3) are the major stabilizing structures in proteins. In peptides, the classification of secondary regular structures is more complex, and is related to the hydrogen bond pattern that stabilizes the structure (5). An H bond between N-H of an amino acid sequence number m, and C = O of a residue of the sequence number n is designated as m→n (Fig. 4). Then, the possible structures in the systems of four linked peptide units are the 2→2 (or 3→3, or 4→4), the 2→3 (or 3→4), the 2→4, the 3→1 (or 4→2or5→3), the 4→1 (or 5→2), and the 5→1 intramolecular H-bonded conformations. On the basis of the number of atoms in the ring formed by closing the H-bond, the aforementioned conformations are also called the C5,C8,C11,C7,C10, and C13 conformations. The C5 conformation is extended, and the others are of the folded type. A nomenclature of common use for C7,C8,C10,C11, and C13 conformations is γ-, δ-, β-, ε-, and α-turn, respectively. The C8, C10, C11, ad C13 forms may include cis peptide configurations. The presence of consecutive α-turns or β-turns gives rise to α-helical or 310 helix secondary structures, respectively.
Mammalian Allergens
Published in Richard F. Lockey, Dennis K. Ledford, Allergens and Allergen Immunotherapy, 2014
Tuomas Virtanen, Tuure Kinnunen, Marja Rytkönen-Nissinen
Despite the low sequential identity, lipocalins share a common three-dimensional structure (Figure 15.3).14 The central β-barrel of lipocalins is composed of eight antiparallel β-strands, and it encloses an internal ligand-binding site (Figures 15.2 and 15.3). At the N-terminus, there is a 310 helix, whereas at the C-terminus, there is an α-helix of variable length. The oligomerization (arrangement in multisubunit complexes) of lipocalins is variable (Table 15.1). The three-dimensional structures of several lipocalin allergens are known (Table 15.1).
Advances in the structural characterization of complexes of therapeutic antibodies with PD-1 or PD-L1
Published in mAbs, 2023
Mengzhen Jiang, Man Liu, Guodi Liu, Jiawen Ma, Lixin Zhang, Shenlin Wang
Nanobodies are highly stable and easy to produce in high yields through simple bacterial expression systems, making them a promising tool for research and treatment.154 Envafolimab (KN035) was developed by Alphamab Oncology and approved by NMPA in 2021 for advanced biliary tract cancer and soft tissue sarcoma. It was the first and currently the only nanobody approved as a cancer therapeutic. Zhou and colleagues of Alphamab Oncology47 obtained KN035 by immunizing camels with human PD-L1 and screening a VH-only nanobody phage library. Subsequently, the structure of KN035-PD-L1 complex was determined. It revealed that KN035 has three CDR loops (CDR1, CDR2 and CDR3),155,156 and that CDR1 folds into a short α helix, whereas CDR3 contains a short α helix and a 310 helix. A disulfide bond connects the short α helix of CDR3 to CDR1, and another disulfide bond connects the B and F chains of KN035 (Figure 10).
Molecular dynamics simulations and novel drug discovery
Published in Expert Opinion on Drug Discovery, 2018
Xuewei Liu, Danfeng Shi, Shuangyan Zhou, Hongli Liu, Huanxiang Liu, Xiaojun Yao
Amyloid deposits of prion protein (PrP) are the hallmark of multiple neurodegenerative diseases, such as Gerstmann-Sträussler-Scheinker (GSS), Creutzfeldt-Jakob disease (CJD), bovine spongiform encephalopathy (BSE) [36,65,66]. The structure of PrP can be divided into two parts, a structured global C-terminal region (121–231) and a flexible disordered N-terminal tail (23–120). It is reported that the conformational transition from the cellular PrPC to the abnormal PrPSc is the main cause of prion diseases [67]. Prion diseases can occur spontaneously, be transmitted from infected individuals, or be obtained from familial mutations. In humans, over 30 different point mutations have been reported to correlate with familial CJD, fatal familial insomnia (FFI), and so on [68]. These single point mutations can distinctly affect the structural stability and kinetic properties of prion. Many works have focused on exploring the effects of pathogenic mutations on the structure of PrP by MD methods [69–72]. The simulation study by van der Kamp et al. indicated that several pathogenic mutations in the hydrophobic core (V180I, F198S, V203I, and V210I) of human PrP (huPrP) can reduce the structural stability and promote the misfolding of huPrP [73]. Chen et al. studied three mutations in the first strand of the native β-sheet in huPrP: G131V, S132I, and A133V [74]. Their simulation results indicated that these mutations induced different effects on the native β-sheet: G131V elongated the native β-sheet, A133V disrupted the native β-sheet, and S132I converted the native β-sheet into an α-sheet. We also studied the effects of several pathogenic mutants on PrPC by performing MD simulations, including D202N, E211Q, and Q217 located in helix 3 of huPrP and T188K/R/A at residue 188 located in helix 2 [75,76]. The results indicated that the three mutations D202N, E211Q, and Q217 had subtle effects on the whole protein structures but showed large influences in the overall electrostatic potential distributions [75]. For T188K/R/A, the three mutations had diverse effects on the dynamic properties of PrP, including the shift of H1, the elongation of the native β-sheet, and the conversion of S2-H2 loop to a 310 helix, although the globular domains were fairly conserved [76].