Predicting and harnessing protein flexibility in the design of species-specific inhibitors of thymidylate synthase1,21Escherichia coli thymidylate synthase numbering is used unless otherwise noted.2PDB coordinates have been deposited with the RCSB with accession ID: 1JG0.

AbstractCrystal structures were solved of the binary complexes Trichinella spiralis and Caenorhabditis elegans thymidylate synthases with deoxyuridine monophosphate (dUMP), with crystals obtained by the vapor diffusion method in hanging drops. For the T. spiralis thymidylate synthase-dUMP complex, the diffraction data were collected at the BESSY Synchrotron to 1.9 Å resolution. The crystal belongs to the space group P1 with two dimers in the asymmetric unit (ASU). For the C. elegans TS-dUMP complex crystal, the diffraction data were collected at the BESSY Synchrotron to 2.48 Å resolution, and the crystal belongs to the space group P 32 2 1, with two monomers (one dimer) in the ASU. Structural comparisons were made of both structures and each of them with the corresponding mouse thymidylate synthase complex.

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Identification, Biochemical and Structural Evaluation of Species-Specific Inhibitors against Type I Methionine Aminopeptidases

Journal of Medicinal Chemistry ◽

10.1021/jm400395p ◽

2013 ◽

Vol 56 (13) ◽

pp. 5295-5305 ◽

Cited By ~ 17

Author(s):

Chandan Kishor ◽

Tarun Arya ◽

Ravikumar Reddi ◽

Xiaochun Chen ◽

Venkateshwarlu Saddanapu ◽

...

Keyword(s):

Type I ◽

Methionine Aminopeptidases ◽

Structural Evaluation ◽

Species Specific ◽

Specific Inhibitors

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ortho-Halogen naphthaleins as specific inhibitors of Lactobacillus casei thymidylate synthase. Conformational properties and biological activity

Bioorganic & Medicinal Chemistry ◽

10.1016/s0968-0896(02)00541-2 ◽

2003 ◽

Vol 11 (6) ◽

pp. 951-963 ◽

Cited By ~ 6

Author(s):

Stefano Ghelli ◽

Marcella Rinaldi ◽

Daniela Barlocco ◽

Arianna Gelain ◽

Piergiorgio Pecorari ◽

...

Keyword(s):

Biological Activity ◽

Thymidylate Synthase ◽

Lactobacillus Casei ◽

Conformational Properties ◽

Specific Inhibitors

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Structural studies provide clues for analog design of specific inhibitors of Cryptosporidium hominis thymidylate synthase–dihydrofolate reductase

Bioorganic & Medicinal Chemistry Letters ◽

10.1016/j.bmcl.2014.07.049 ◽

2014 ◽

Vol 24 (17) ◽

pp. 4158-4161 ◽

Cited By ~ 19

Author(s):

Vidya P. Kumar ◽

Jose A. Cisneros ◽

Kathleen M. Frey ◽

Alejandro Castellanos-Gonzalez ◽

Yiqiang Wang ◽

...

Keyword(s):

Dihydrofolate Reductase ◽

Thymidylate Synthase ◽

Analog Design ◽

Structural Studies ◽

Cryptosporidium Hominis ◽

Specific Inhibitors

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Structure-based studies on species-specific inhibition of thymidylate synthase

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease ◽

10.1016/s0925-4439(02)00083-2 ◽

2002 ◽

Vol 1587 (2-3) ◽

pp. 206-214 ◽

Cited By ~ 25

Author(s):

M.Paola Costi ◽

Donatella Tondi ◽

Marcella Rinaldi ◽

Daniela Barlocco ◽

Piergiorgio Pecorari ◽

...

Keyword(s):

Thymidylate Synthase ◽

Specific Inhibition ◽

Species Specific

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Identification of enzymes that are required for Rhodoquinone-dependent metabolism as targets for new species-specific inhibitors

10.1101/2021.03.24.436840 ◽

2021 ◽

Author(s):

Margot J. Lautens ◽

June H. Tan ◽

Xènia Serrat ◽

Samantha Del Borrello ◽

Michael R. Schertzberg ◽

...

Keyword(s):

New Species ◽

Active Sites ◽

Anaerobic Metabolism ◽

Kynurenine Pathway ◽

New Drugs ◽

Human Pathogens ◽

High Confidence ◽

Species Specific ◽

Druggable Targets ◽

Specific Inhibitors

ABSTRACTSoil transmitted helminths (STHs) are major human pathogens that infect over a billion people. Resistance to current anthelmintics is rising and new drugs are needed. Here we combine multiple approaches to find druggable targets that are essential for RQ-dependent metabolism, an unusual form of anaerobic metabolism which STHs need to survive in their host. We identified 25 genes predicted to act in RQ-dependent metabolism from sensing hypoxia to RQ synthesis — this includes components of the kynurenine pathway we previously showed to be essential for RQ synthesis (Del Borrello et al., 2019). We found 9 genes to be required — since all have host orthologues, we used comparative genomics and structural modeling to identify those with helminth-specific active sites and found 4 such targets. These 4 high confidence targets open up the possibility of in silico screens to identify STH-specific inhibitors of these enzymes as new anthelmintics.

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Electron Microscopy in the Study of Natural Phytoplankton Assemblages

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100119831 ◽

1985 ◽

Vol 43 ◽

pp. 620-623

Author(s):

Linda Sicko-Goad

Keyword(s):

Electron Microscopy ◽

Aquatic Environment ◽

Size Range ◽

Physical Parameters ◽

Specific Information ◽

Phytoplankton Assemblages ◽

Phytoplankton Productivity ◽

Ecosystem Effects ◽

Time Of Year ◽

Species Specific

Although the use of electron microscopy and its varied methodologies is not usually associated with ecological studies, the types of species specific information that can be generated by these techniques are often quite useful in predicting long-term ecosystem effects. The utility of these techniques is especially apparent when one considers both the size range of particles found in the aquatic environment and the complexity of the phytoplankton assemblages.The size range and character of organisms found in the aquatic environment are dependent upon a variety of physical parameters that include sampling depth, location, and time of year. In the winter months, all the Laurentian Great Lakes are uniformly mixed and homothermous in the range of 1.1 to 1.7°C. During this time phytoplankton productivity is quite low.

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