scholarly journals Solution structure of family 21 carbohydrate-binding module from Rhizopus oryzae glucoamylase

2007 ◽  
Vol 403 (1) ◽  
pp. 21-30 ◽  
Author(s):  
Yu-Nan Liu ◽  
Yen-Ting Lai ◽  
Wei-I Chou ◽  
Margaret Dah-Tsyr Chang ◽  
Ping-Chiang Lyu
Keyword(s):  
Amino Acid ◽  
Chemical Shift ◽  
Ligand Binding ◽  
Solution Structure ◽  
Rhizopus Oryzae ◽  
Carbohydrate Binding ◽  
Type I ◽  
Type Ii ◽  
Sequence Motifs ◽  
Carbohydrate Binding Modules

CBMs (carbohydrate-binding modules) function independently to assist carbohydrate-active enzymes. Family 21 CBMs contain approx. 100 amino acid residues, and some members have starchbinding functions or glycogen-binding activities. We report here the first structure of a family 21 CBM from the SBD (starch-binding domain) of Rhizopus oryzae glucoamylase (RoCBM21) determined by NMR spectroscopy. This CBM has a β-sandwich fold with an immunoglobulin-like structure. Ligand-binding properties of RoCBM21 were analysed by chemical-shift perturbations and automated docking. Structural comparisons with previously reported SBDs revealed two types of topologies, namely type I and type II, with CBM20, CBM25, CBM26 and CBM41 showing type I topology, with CBM21 and CBM34 showing type II topology. According to the chemical-shift perturbations, RoCBM21 contains two ligand-binding sites. Residues in site II are similar to those found in the family 20 CBM from Aspergillus niger glucoamylase (AnCBM20). Site I, however, is embedded in a region with unique sequence motifs only found in some members of CBM21s. Additionally, docking of β-cyclodextrin and malto-oligosaccharides highlights that side chains of Y83 and W47 (one-letter amino acid code) form the central part of the conserved binding platform in the SBD. The structure of RoCBM21 provides the first direct evidence of the structural features and the basis for protein–carbohydrate recognition from an SBD of CBM21.

scholarly journals Structure-based mapping of the TβRI and TβRII receptor binding sites of the parasitic TGF-β mimic, Hp-TGM

2020 ◽  
Author(s):  
Ananya Mukundan ◽  
Chang-Hyeock Byeon ◽  
Cynthia S. Hinck ◽  
Danielle J. Smyth ◽  
Rick M. Maizels ◽  
...  
Keyword(s):  
T Cells ◽  
Chemical Shift ◽  
Solution Structure ◽  
Adaptive Immune System ◽  
Structural Similarity ◽  
Binary Complex ◽  
Type I ◽  
Type Ii ◽  
Nmr Chemical Shift ◽  
Heligmosomoides Polygyrus

AbstractTGF-β is a secreted signaling protein involved in many physiological processes: organ development, production and maintenance of the extracellular matrix, as well as regulation of the adaptive immune system. As a cytokine, TGF-β stimulates the differentiation of CD4+ T-cells into regulatory T-cells (Tregs) that act to promote peripheral immune tolerance. The murine parasite Heligmosomoides polygyrus takes advantage of this pathway to induce inducing Foxp3+ Tregs in a similar manner using a TGF-β mimic (TGM), comprised of five tandem complement control protein (CCP) domains, designated D1-D5. Despite having no structural homology to TGF-β or to TGF-β family proteins, TGM binds directly to the TGF-β type I and type II receptors, TβRI and TβRII. To further investigate, NMR titration, and SPR and ITC binding experiments were performed, showing that TGM-D2, with the aid of D1, binds TβRI and TGM-D3 binds TβRII. Competition ITC experiments showed that TGM-D3 competes with TGF-β for binding to TβRII, consistent with TGM-D3-induced NMR chemical shift perturbations of TβRII which aligned with the solvent inaccessible areas of TβRII upon binding TGF-β. Thus, TGM-D3 binds to the same edged β-strand of TβRII that is used to bind TGF-β. Competition ITC experiments demonstrated that TGM-D1D2 and TGF-β3:TβRII compete for binding to TβRI, while TGM-D2-induced NMR chemical shift perturbation of TβRI showed that TGM-D2 binds to the same pre-helix extension of TβRI as does the TGF-β/TβRII binary complex. The solution structure of TGM-D3 revealed that while it has the overall structure of a CCP domain, TGM-D3 has an insertion in the hypervariable loop uncommon to CCP domains. These findings suggest that parasitic TGM, despite its lack of structural similarity to TGF-β, evolved to take advantage of the binding regions of the mammalian TGF-β type I and type II receptors. The structure of this TGM domain, along with the predicted structure of other H. polygyrus secreted proteins reported in the literature, suggest that TGM is part of a larger family of evolutionarily-adapted immunomodulatory CCP-containing proteins.

scholarly journals Mutational Insights into the Roles of Amino Acid Residues in Ligand Binding for Two Closely Related Family 16 Carbohydrate Binding Modules

2010 ◽  
Vol 285 (45) ◽  
pp. 34665-34676 ◽  
Author(s):  
Xiaoyun Su ◽  
Vinayak Agarwal ◽  
Dylan Dodd ◽  
Brian Bae ◽  
Roderick I. Mackie ◽  
...  
Keyword(s):  
Amino Acid ◽  
Ligand Binding ◽  
Carbohydrate Binding ◽  
Amino Acid Residues ◽  
Related Family ◽  
Carbohydrate Binding Modules

scholarly journals Mechanisms of Transforming Growth Factor-β Receptor Endocytosis and Intracellular Sorting Differ between Fibroblasts and Epithelial Cells

2001 ◽  
Vol 12 (3) ◽  
pp. 675-684 ◽  
Author(s):  
Jules J.E. Doré ◽  
Diying Yao ◽  
Maryanne Edens ◽  
Nandor Garamszegi ◽  
Elizabeth L. Sholl ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Ligand Binding ◽  
Transforming Growth Factor ◽  
Point Mutations ◽  
Type I ◽  
Receptor Complex ◽  
Type Ii ◽  
Down Regulation ◽  
Β Receptor

Transforming growth factor-βs (TGF-β) are multifunctional proteins capable of either stimulating or inhibiting mitosis, depending on the cell type. These diverse cellular responses are caused by stimulating a single receptor complex composed of type I and type II receptors. Using a chimeric receptor model where the granulocyte/monocyte colony-stimulating factor receptor ligand binding domains are fused to the transmembrane and cytoplasmic signaling domains of the TGF-β type I and II receptors, we wished to describe the role(s) of specific amino acid residues in regulating ligand-mediated endocytosis and signaling in fibroblasts and epithelial cells. Specific point mutations were introduced at Y182, T200, and Y249 of the type I receptor and K277 and P525 of the type II receptor. Mutation of either Y182 or Y249, residues within two putative consensus tyrosine-based internalization motifs, had no effect on endocytosis or signaling. This is in contrast to mutation of T200 to valine, which resulted in ablation of signaling in both cell types, while only abolishing receptor down-regulation in fibroblasts. Moreover, in the absence of ligand, both fibroblasts and epithelial cells constitutively internalize and recycle the TGF-β receptor complex back to the plasma membrane. The data indicate fundamental differences between mesenchymal and epithelial cells in endocytic sorting and suggest that ligand binding diverts heteromeric receptors from the default recycling pool to a pathway mediating receptor down-regulation and signaling.

scholarly journals Biochemical and structural characterization of the novel sialic acid-binding site of Escherichia coli heat-labile enterotoxin LT-IIb

2016 ◽  
Vol 473 (21) ◽  
pp. 3923-3936 ◽  
Author(s):  
Dani Zalem ◽  
João P. Ribeiro ◽  
Annabelle Varrot ◽  
Michael Lebens ◽  
Anne Imberty ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Binding Site ◽  
Cholera Toxin ◽  
Carbohydrate Binding ◽  
Type I ◽  
Type Ii ◽  
E Coli ◽  
B Subunit ◽  
Heat Labile ◽  
B Subunits

The structurally related AB5-type heat-labile enterotoxins of Escherichia coli and Vibrio cholerae are classified into two major types. The type I group includes cholera toxin (CT) and E. coli LT-I, whereas the type II subfamily comprises LT-IIa, LT-IIb and LT-IIc. The carbohydrate-binding specificities of LT-IIa, LT-IIb and LT-IIc are distinctive from those of cholera toxin and E. coli LT-I. Whereas CT and LT-I bind primarily to the GM1 ganglioside, LT-IIa binds to gangliosides GD1a, GD1b and GM1, LT-IIb binds to the GD1a and GT1b gangliosides, and LT-IIc binds to GM1, GM2, GM3 and GD1a. These previous studies of the binding properties of type II B-subunits have been focused on ganglio core chain gangliosides. To further define the carbohydrate binding specificity of LT-IIb B-subunits, we have investigated its binding to a collection of gangliosides and non-acid glycosphingolipids with different core chains. A high-affinity binding of LT-IIb B-subunits to gangliosides with a neolacto core chain, such as Neu5Gcα3- and Neu5Acα3-neolactohexaosylceramide, and Neu5Gcα3- and Neu5Acα3-neolactooctaosylceramide was detected. An LT-IIb-binding ganglioside was isolated from human small intestine and characterized as Neu5Acα3-neolactohexaosylceramide. The crystal structure of the B-subunit of LT-IIb with the pentasaccharide moiety of Neu5Acα3-neolactotetraosylceramide (Neu5Ac-nLT: Neu5Acα3Galβ4GlcNAcβ3Galβ4Glc) was determined providing the first information for a sialic-binding site in this subfamily, with clear differences from that of CT and LT-I.

scholarly journals The Location of the Ligand-binding Site of Carbohydrate-binding Modules That Have Evolved from a Common Sequence Is Not Conserved

2001 ◽  
Vol 276 (51) ◽  
pp. 48580-48587 ◽  
Author(s):  
Mirjam Czjzek ◽  
David N. Bolam ◽  
Amor Mosbah ◽  
Julie Allouch ◽  
Carlos M. G. A. Fontes ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Binding Site ◽  
Carbohydrate Binding ◽  
Ligand Binding Site ◽  
Carbohydrate Binding Modules ◽  
Common Sequence

scholarly journals Seven new mutations in the nicotinamide adenine dinucleotide reduced–cytochrome b5 reductase gene leading to methemoglobinemia type I

Blood ◽  
2001 ◽  
Vol 97 (4) ◽  
pp. 1106-1114 ◽  
Author(s):  
Jan Dekker ◽  
Michel H. M. Eppink ◽  
Rob van Zwieten ◽  
Thea de Rijk ◽  
Angel F. Remacha ◽  
...  
Keyword(s):  
Amino Acid ◽  
Nicotinamide Adenine Dinucleotide ◽  
Cytochrome B5 ◽  
Enzyme Inactivation ◽  
Amino Acid Substitutions ◽  
Type I ◽  
Type Ii ◽  
3 Dimensional ◽  
Cytochrome B5 Reductase ◽  
Fad Binding

Abstract Cytochrome b5 reductase (b5R) deficiency manifests itself in 2 distinct ways. In methemoglobinemia type I, the patients only suffer from cyanosis, whereas in type II, the patients suffer in addition from severe mental retardation and neurologic impairment. Biochemical data indicate that this may be due to a difference in mutations, causing enzyme instability in type I and complete enzyme deficiency or enzyme inactivation in type II. We have investigated 7 families with methemoglobulinemia type I and found 7 novel mutations in the b5R gene. Six of these mutations predicted amino acid substitutions at sites not involved in reduced nicotinamide adenine dinucleotide (NADH) or flavin adenine dinucleotide (FAD) binding, as deduced from a 3-dimensional model of human b5R. This model was constructed from comparison with the known 3-dimensional structure of pig b5R. The seventh mutation was a splice site mutation leading to skipping of exon 5 in messenger RNA, present in heterozygous form in a patient together with a missense mutation on the other allele. Eight other amino acid substitutions, previously described to cause methemoglobinemia type I, were also situated in nonessential regions of the enzyme. In contrast, 2 other substitutions, known to cause the type II form of the disease, were found to directly affect the consensus FAD-binding site or indirectly influence NADH binding. Thus, these data support the idea that enzyme inactivation is a cause of the type II disease, whereas enzyme instability may lead to the type I form.

NMR Solution Structure of Type II Human Cellular Retinoic Acid Binding Protein:  Implications for Ligand Binding†,‡

Biochemistry ◽  
1998 ◽  
Vol 37 (37) ◽  
pp. 12727-12736 ◽  
Author(s):  
Lincong Wang ◽  
Yue Li ◽  
Frits Abildgaard ◽  
John L. Markley ◽  
Honggao Yan
Keyword(s):  
Retinoic Acid ◽  
Ligand Binding ◽  
Solution Structure ◽  
Binding Protein ◽  
Type Ii ◽  
Nmr Solution Structure ◽  
Acid Binding Protein

Pyrophosphates of Tetravalent Elements and a Mössbauer Study of SnP2O7

1975 ◽  
Vol 53 (1) ◽  
pp. 79-91 ◽  
Author(s):  
Chung-Hsi Huang ◽  
Osvald Knop ◽  
David A. Othen ◽  
Frank W. D. Woodhams ◽  
R. Allan Howie
Keyword(s):  
Chemical Shift ◽  
Electric Field ◽  
Electric Field Gradient ◽  
The Other ◽  
Type I ◽  
Type Ii ◽  
Transition Elements ◽  
Mössbauer Study ◽  
X Ray ◽  
Ionic Compounds

Cubic M4+P2O7 pyrophosphates of Ti, Zr, Hf, Sn, and Pb have been examined by X-ray powder diffractometry and by infrared, Raman, and Mössbauer 119Sn spectroscopy. The tin compound appeared to be of Chaunac's type I (with P2O7 groups oriented at random) and could be converted to type II (with ordered P2O7 groups) by heating to high temperatures. All the other preparations were of Chaunac's type II. Evidence from lattice parameters and intensity features of the Raman spectra suggests that the cubic MP2O7 pyrophosphates fall in two groups, one containing the compounds of the typical elements (Ge, Sn, Pb) and the other, the compounds of the transition elements. No support has been found for the view that the P—O—P groupings of the pyrophosphate anion in these compounds are linear. The 119Sn chemical shift in SnP2O7 is only slightly less negative than the shift in CuSnF6.4H2O, which makes SnP2O7 one of the most ionic compounds of tetravalent tin known. The observed quadrupole splitting in the Mössbauer spectrum of SnP2O7 arises largely from the contribution of the valence term to the electric field gradient at the Sn atom.

Solution Structure of the Chick TGFβ Type II Receptor Ligand-binding Domain

2003 ◽  
Vol 326 (4) ◽  
pp. 989-997 ◽  
Author(s):  
Michael S. Marlow ◽  
Christopher B. Brown ◽  
Joey V. Barnett ◽  
Andrzej M. Krezel
Keyword(s):  
Ligand Binding ◽  
Solution Structure ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Type Ii ◽  
Receptor Ligand
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