Structure-Based Design, Synthesis, and X-ray Crystallography of a High-Affinity Antagonist of the Grb2-SH2 Domain Containing an Asparagine Mimetic

1999 ◽  
Vol 42 (13) ◽  
pp. 2358-2363 ◽  
Author(s):  
Pascal Furet ◽  
Carlos García-Echeverría ◽  
Brigitte Gay ◽  
Joseph Schoepfer ◽  
Martin Zeller ◽  
...  
Keyword(s):  
Sh2 Domain ◽  
Design Synthesis ◽  
X Ray ◽  
X Ray Crystallography ◽  
High Affinity

Design, synthesis, and kinetic evaluation of high-affinity FKBP ligands and the X-ray crystal structures of their complexes with FKBP12

1993 ◽  
Vol 115 (22) ◽  
pp. 9925-9938 ◽  
Author(s):  
Dennis A. Holt ◽  
Juan I. Luengo ◽  
Dennis S. Yamashita ◽  
Hye Ja Oh ◽  
Arda L. Konialian ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Design Synthesis ◽  
Kinetic Evaluation ◽  
X Ray ◽  
High Affinity

scholarly journals High-Affinity IgE Recognition of a Conformational Epitope of the Major Respiratory Allergen Phl p 2 As Revealed by X-Ray Crystallography

2009 ◽  
Vol 182 (4) ◽  
pp. 2141-2151 ◽  
Author(s):  
Sivaraman Padavattan ◽  
Sabine Flicker ◽  
Tilman Schirmer ◽  
Christoph Madritsch ◽  
Stefanie Randow ◽  
...  
Keyword(s):  
Conformational Epitope ◽  
X Ray ◽  
X Ray Crystallography ◽  
High Affinity

scholarly journals MBP-binding DARPins facilitate the crystallization of an MBP fusion protein

2018 ◽  
Vol 74 (9) ◽  
pp. 549-557 ◽  
Author(s):  
Rajesh Gumpena ◽  
George T. Lountos ◽  
David S. Waugh
Keyword(s):  
Fusion Protein ◽  
Catalytic Domain ◽  
Fusion Partner ◽  
High Quality ◽  
X Ray ◽  
X Ray Crystallography ◽  
High Affinity ◽  
Repeat Proteins ◽  
Dual Specificity ◽  
Ankyrin Repeat Proteins

The production of high-quality crystals is the main bottleneck in determining the structures of proteins using X-ray crystallography. In addition to being recognized as a very effective solubility-enhancing fusion partner,Escherichia colimaltose-binding protein (MBP) has also been successfully employed as a `fixed-arm' crystallization chaperone in more than 100 cases. Here, it is reported that designed ankyrin-repeat proteins (DARPins) that bind with high affinity to MBP can promote the crystallization of an MBP fusion protein when the fusion protein alone fails to produce diffraction-quality crystals. As a proof of principle, three different co-crystal structures of MBP fused to the catalytic domain of human dual-specificity phosphatase 1 in complex with DARPins are reported.

scholarly journals High Consistency of Structure-Based Design and X-Ray Crystallography: Design, Synthesis, Kinetic Evaluation and Crystallographic Binding Mode Determination of Biphenyl-N-acyl-β-d-Glucopyranosylamines as Glycogen Phosphorylase Inhibitors

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1322 ◽  
Author(s):  
Thomas Fischer ◽  
Symeon M. Koulas ◽  
Anastasia S. Tsagkarakou ◽  
Efthimios Kyriakis ◽  
George A. Stravodimos ◽  
...  
Keyword(s):  
Glycogen Phosphorylase ◽  
Catalytic Mechanism ◽  
Liver Glycogen ◽  
Binding Mode ◽  
Structural Water ◽  
Design Synthesis ◽  
Kinetic Evaluation ◽  
X Ray ◽  
X Ray Crystallography ◽  
Design And Synthesis

Structure-based design and synthesis of two biphenyl-N-acyl-β-d-glucopyranosylamine derivatives as well as their assessment as inhibitors of human liver glycogen phosphorylase (hlGPa, a pharmaceutical target for type 2 diabetes) is presented. X-ray crystallography revealed the importance of structural water molecules and that the inhibitory efficacy correlates with the degree of disturbance caused by the inhibitor binding to a loop crucial for the catalytic mechanism. The in silico-derived models of the binding mode generated during the design process corresponded very well with the crystallographic data.

scholarly journals Design, synthesis and X-ray crystallography of selenides bearing benzenesulfonamide moiety with neuropathic pain modulating effects

2018 ◽  
Vol 154 ◽  
pp. 210-219 ◽  
Author(s):  
Andrea Angeli ◽  
Lorenzo di Cesare Mannelli ◽  
Elena Lucarini ◽  
Thomas S. Peat ◽  
Carla Ghelardini ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Design Synthesis ◽  
X Ray ◽  
X Ray Crystallography

A New, Simple, High-Affinity Glycosidase Inhibitor:  Analysis of Binding through X-ray Crystallography, Mutagenesis, and Kinetic Analysis

2000 ◽  
Vol 122 (17) ◽  
pp. 4229-4230 ◽  
Author(s):  
Spencer J. Williams ◽  
Valerie Notenboom ◽  
Jacqueline Wicki ◽  
David R. Rose ◽  
Stephen G. Withers
Keyword(s):  
Kinetic Analysis ◽  
X Ray ◽  
X Ray Crystallography ◽  
High Affinity ◽  
Inhibitor Analysis ◽  
Glycosidase Inhibitor

Design, synthesis, structure-activity relationships study and X-ray crystallography of 3-substituted-indolin-2-one-5-carboxamide derivatives as PAK4 inhibitors

2018 ◽  
Vol 155 ◽  
pp. 197-209 ◽  
Author(s):  
Jing Guo ◽  
Fan Zhao ◽  
Wenbo Yin ◽  
Mingyue Zhu ◽  
Chenzhou Hao ◽  
...  
Keyword(s):  
Design Synthesis ◽  
X Ray ◽  
Structure Activity Relationships ◽  
X Ray Crystallography ◽  
Structure Activity

scholarly journals Mutation of High-Affinity Methionine Permease Contributes to Selenomethionyl Protein Production in Saccharomyces cerevisiae

2010 ◽  
Vol 76 (19) ◽  
pp. 6351-6359 ◽  
Author(s):  
Toshihiko Kitajima ◽  
Yasunori Chiba ◽  
Yoshifumi Jigami
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Methylotrophic Yeast ◽  
Culture Conditions ◽  
Crystallographic Analysis ◽  
Gene Encoding ◽  
X Ray ◽  
X Ray Crystallography ◽  
High Affinity ◽  
Standard Culture ◽  
Resistant Mutants

ABSTRACT The production of selenomethionine (SeMet) derivatives of recombinant proteins allows phase determination by single-wavelength or multiwavelength anomalous dispersion phasing in X-ray crystallography, and this popular approach has permitted the crystal structures of numerous proteins to be determined. Although yeast is an ideal host for the production of large amounts of eukaryotic proteins that require posttranslational modification, the toxic effects of SeMet often interfere with the preparation of protein derivatives containing this compound. We previously isolated a mutant strain (SMR-94) of the methylotrophic yeast Pichia pastoris that is resistant to both SeMet and selenate and demonstrated its applicability for the production of proteins suitable for X-ray crystallographic analysis. However, the molecular basis for resistance to SeMet by the SMR-94 strain remains unclear. Here, we report the characterization of SeMet-resistant mutants of Saccharomyces cerevisiae and the identification of a mutant allele of the MUP1 gene encoding high-affinity methionine permease, which confers SeMet resistance. Although the total methionine uptake by the mup1 mutant (the SRY5-7 strain) decreased to 47% of the wild-type level, it was able to incorporate SeMet into the overexpressed epidermal growth factor peptide with 73% occupancy, indicating the importance of the moderate uptake of SeMet by amino acid permeases other than Mup1p for the alleviation of SeMet toxicity. In addition, under standard culture conditions, the mup1 mutant showed higher productivity of the SeMet derivative relative to other SeMet-resistant mutants. Based on these results, we conclude that the mup1 mutant would be useful for the preparation of selenomethionyl proteins for X-ray crystallography.

scholarly journals High Consistency of Structure-Based Design and X-Ray Crystallography: Design, Synthesis, Kinetic Evaluation and Crystallographic Binding Mode Determination of Biphenyl-N-Acyl-β-D-Glucopyranosylamines as Glycogen Phosphorylase Inhibitors

2019 ◽  
Author(s):  
Thomas Fischer ◽  
Symeon M. Koulas ◽  
Anastasia S. Tsagkarakou ◽  
Efthimios Kyriakis ◽  
George A. Stravodimos ◽  
...  
Keyword(s):  
Glycogen Phosphorylase ◽  
Catalytic Mechanism ◽  
Liver Glycogen ◽  
Binding Mode ◽  
Structural Water ◽  
Design Synthesis ◽  
Kinetic Evaluation ◽  
X Ray ◽  
X Ray Crystallography ◽  
Design And Synthesis

Structure-based design and synthesis of two biphenyl-N-acyl-β-D-glucopyranosylamine derivatives as well as their assessment as inhibitors of human liver glycogen phosphorylase (hlGPa, a pharmaceutical target for type 2 diabetes) is presented. X-ray crystallography revealed the importance of structural water molecules and that the inhibitory efficacy correlates with the degree of disturbance caused by the inhibitor binding to a loop crucial for the catalytic mechanism. The in silico derived models of the binding mode generated during the design process corresponded very well with the crystallographic data.

scholarly journals Novel Tacrine–Benzofuran Hybrids as Potent Multitarget-Directed Ligands for the Treatment of Alzheimer’s Disease: Design, Synthesis, Biological Evaluation, and X-ray Crystallography

2015 ◽  
Vol 59 (1) ◽  
pp. 114-131 ◽  
Author(s):  
Xiaoming Zha ◽  
Doriano Lamba ◽  
Lili Zhang ◽  
Yinghan Lou ◽  
Changxu Xu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
X Ray ◽  
X Ray Crystallography
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