Crystal Structures of Class C β-Lactamases: Mechanistic Implications and Perspectives in Drug Design

2014 ◽  
pp. 145-161 ◽  
Author(s):  
C. Bauvois ◽  
J. Wouters
Keyword(s):  
Drug Design ◽  
Crystal Structures ◽  
Class C

scholarly journals Structural insights into targeting of the colchicine binding site by ELR510444 and parbendazole to achieve rational drug design

RSC Advances ◽  
2021 ◽  
Vol 11 (31) ◽  
pp. 18938-18944
Author(s):  
Jia-Hong Lei ◽  
Ling-Ling Ma ◽  
Jing-Hong Xian ◽  
Hai Chen ◽  
Jian-Jian Zhou ◽  
...  
Keyword(s):  
Drug Design ◽  
Binding Site ◽  
Crystal Structures ◽  
Rational Drug Design ◽  
Colchicine Binding Site ◽  
Rational Drug ◽  
Structural Insights

Crystal structures of tubulin complexed with ELR510444 and parbendazole facilitate the design of novel colchicine binding site inhibitors.

Librarians, crystal structures and drug design

2005 ◽  
pp. 5135 ◽  
Author(s):  
Frank H. Allen ◽  
Robin Taylor
Keyword(s):  
Drug Design ◽  
Crystal Structures

scholarly journals Structure of human tankyrase 1 in complex with small-molecule inhibitors PJ34 and XAV939

2012 ◽  
Vol 68 (2) ◽  
pp. 115-118 ◽  
Author(s):  
Christina A. Kirby ◽  
Atwood Cheung ◽  
Aleem Fazal ◽  
Michael D. Shultz ◽  
Travis Stams
Keyword(s):  
Drug Design ◽  
Crystal Structures ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Donor Site ◽  
Structure Based Drug Design ◽  
Crystallization System ◽  
Tankyrase 1

The crystal structures of tankyrase 1 (TNKS1) in complex with two small-molecule inhibitors, PJ34 and XAV939, both at 2.0 Å resolution, are reported. The structure of TNKS1 in complex with PJ34 reveals two molecules of PJ34 bound in the NAD+donor pocket. One molecule is in the nicotinamide portion of the pocket, as previously observed in other PARP structures, while the second molecule is bound in the adenosine portion of the pocket. Additionally, unlike the unliganded crystallization system, the TNKS1–PJ34 crystallization system has the NAD+donor site accessible to bulk solvent in the crystal, which allows displacement soaking. The TNKS1–PJ34 crystallization system was used to determine the structure of TNKS1 in complex with XAV939. These structures provide a basis for the start of a structure-based drug-design campaign for TNKS1.

scholarly journals Crystal Structures of HIV-1 Reverse Transcriptase with Picomolar Inhibitors Reveal Key Interactions for Drug Design

2012 ◽  
Vol 134 (48) ◽  
pp. 19501-19503 ◽  
Author(s):  
Kathleen M. Frey ◽  
Mariela Bollini ◽  
Andrea C. Mislak ◽  
José A. Cisneros ◽  
Ricardo Gallardo-Macias ◽  
...  
Keyword(s):  
Drug Design ◽  
Reverse Transcriptase ◽  
Crystal Structures ◽  
Hiv 1

scholarly journals Crystal structures of human ENPP1 in apo and bound forms

2020 ◽  
Vol 76 (9) ◽  
pp. 889-898 ◽  
Author(s):  
Matthew L. Dennis ◽  
Janet Newman ◽  
Olan Dolezal ◽  
Meghan Hattarki ◽  
Regina N. Surjadi ◽  
...  
Keyword(s):  
Immune System ◽  
Drug Design ◽  
Crystal Structures ◽  
Cyclic Gmp ◽  
Therapeutic Target ◽  
Structure Based Drug Design ◽  
X Ray ◽  
Crystallization System ◽  
Causes Of Mortality ◽  
Cancerous Cells

Cancer is one of the leading causes of mortality in humans, and recent work has focused on the area of immuno-oncology, in which the immune system is used to specifically target cancerous cells. Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is an emerging therapeutic target in human cancers owing to its role in degrading cyclic GMP-AMP (cGAMP), an agonist of the stimulator of interferon genes (STING). The available structures of ENPP1 are of the mouse enzyme, and no structures are available with anything other than native nucleotides. Here, the first X-ray crystal structures of the human ENPP1 enzyme in an apo form, with bound nucleotides and with two known inhibitors are presented. The availability of these structures and a robust crystallization system will allow the development of structure-based drug-design campaigns against this attractive cancer therapeutic target.

scholarly journals Crystal structures of Triosephosphate Isomerases from Taenia solium and Schistosoma mansoni provide insights for vaccine rationale and drug design against helminth parasites

2020 ◽  
Vol 14 (1) ◽  
pp. e0007815 ◽  
Author(s):  
Pedro Jimenez-Sandoval ◽  
Eduardo Castro-Torres ◽  
Rogelio González-González ◽  
Corina Díaz-Quezada ◽  
Misraim Gurrola ◽  
...  
Keyword(s):  
Drug Design ◽  
Schistosoma Mansoni ◽  
Crystal Structures ◽  
Taenia Solium ◽  
Helminth Parasites

Glycogen phosphorylase revisited: extending the resolution of the R- and T-state structures of the free enzyme and in complex with allosteric activators

2021 ◽  
Vol 77 (9) ◽  
pp. 303-311
Author(s):  
Demetres D. Leonidas ◽  
Spyros E. Zographos ◽  
Katerina E. Tsitsanou ◽  
Vassiliki T. Skamnaki ◽  
George Stravodimos ◽  
...  
Keyword(s):  
Drug Design ◽  
Binding Site ◽  
Crystal Structures ◽  
Glycogen Phosphorylase ◽  
Structural Features ◽  
Terminal Segment ◽  
Structure Based Drug Design ◽  
Allosteric Transition ◽  
Α Helix ◽  
T State

The crystal structures of free T-state and R-state glycogen phosphorylase (GP) and of R-state GP in complex with the allosteric activators IMP and AMP are reported at improved resolution. GP is a validated pharmaceutical target for the development of antihyperglycaemic agents, and the reported structures may have a significant impact on structure-based drug-design efforts. Comparisons with previously reported structures at lower resolution reveal the detailed conformation of important structural features in the allosteric transition of GP from the T-state to the R-state. The conformation of the N-terminal segment (residues 7–17), the position of which was not located in previous T-state structures, was revealed to form an α-helix (now termed α0). The conformation of this segment (which contains Ser14, phosphorylation of which leads to the activation of GP) is significantly different between the T-state and the R-state, pointing in opposite directions. In the T-state it is packed between helices α4 and α16 (residues 104–115 and 497–508, respectively), while in the R-state it is packed against helix α1 (residues 22′–38′) and towards the loop connecting helices α4′ and α5′ of the neighbouring subunit. The allosteric binding site where AMP and IMP bind is formed by the ordering of a loop (residues 313–326) which is disordered in the free structure, and adopts a conformation dictated mainly by the type of nucleotide that binds at this site.

scholarly journals High-resolution crystal structures of the D1 and D2 domains of protein tyrosine phosphatase epsilon for structure-based drug design

2018 ◽  
Vol 74 (10) ◽  
pp. 1015-1026 ◽  
Author(s):  
George T. Lountos ◽  
Sreejith Raran-Kurussi ◽  
Bryan M. Zhao ◽  
Beverly K. Dyas ◽  
Terrence R. Burke ◽  
...  
Keyword(s):  
Drug Design ◽  
Crystal Structures ◽  
Phosphatase Activity ◽  
Protein Tyrosine Phosphatase ◽  
High Throughput Screening ◽  
Catalytic Domain ◽  
Tyrosine Phosphatase ◽  
Triple Mutant ◽  
Structure Based Drug Design ◽  
Protein Tyrosine

Here, new crystal structures are presented of the isolated membrane-proximal D1 and distal D2 domains of protein tyrosine phosphatase epsilon (PTP∊), a protein tyrosine phosphatase that has been shown to play a positive role in the survival of human breast cancer cells. A triple mutant of the PTP∊ D2 domain (A455N/V457Y/E597D) was also constructed to reconstitute the residues of the PTP∊ D1 catalytic domain that are important for phosphatase activity, resulting in only a slight increase in the phosphatase activity compared with the native D2 protein. The structures reported here are of sufficient resolution for structure-based drug design, and a microarray-based assay for high-throughput screening to identify small-molecule inhibitors of the PTP∊ D1 domain is also described.

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