The crystal structure of human alpha-thrombin in complex with LY178550, a nonpeptidyl, active site-directed inhibitor, has been solved to 2.07 A resolution by the method of X-ray crystallography. The final model of the complex has a crystallographic R-value of 21.5% (Rfree = 23.1%) with 0.014 A and 2.4 degrees standard deviation from ideal bond lengths and angles, respectively. Well-defined electron density was observed for the inhibitor in the active site. The inhibitor binds to the active site in an L-shaped manner, mimicking the bound conformation of the tripeptide arginal series of thrombin inhibitors (Chirgadze NY et al., 1992, American Crystallographic Association Meeting 20: 116 [Abstr. PB311]). The basic amidine of LY178550 forms a salt bridge with Asp 189 within the specificity pocket, while the 4-benzylpiperidine side chain engages in a number of hydrophobic interactions at the S2 and S3 binding sites. The inhibitor does not interact in any fashion with the active site sequence Ser 214-Gly 216, as occurs with many of the inhibitors studied previously. The indole N-H of the inhibitor forms a hydrogen bond to the gamma-oxygen of the catalytic serine (Ser 195).
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http://dx.doi.org/10.1002/pro.5560060705 | DOI Listing |
Proteins
January 2025
Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India.
Vector-borne diseases pose a severe threat to human life, contributing significantly to global mortality. Understanding the structure-function relationship of the vector proteins is pivotal for effective insecticide development due to their involvement in drug resistance and disease transmission. This study reports the structural and dynamic features of D1-like dopamine receptors (DARs) in disease-causing mosquito species, such as Aedes aegypti, Culex quinquefasciatus, Anopheles gambiae, and Anopheles stephensi.
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January 2025
Department of Veterinary Microbiology, West Bengal University of Animal and Fishery Sciences, 37, K.B. Sarani, Belgachia, Kolkata, West Bengal, India.
The study was conducted to detect the occurrence and phenotypic resistance pattern of ESBL-producing Enterobacteriaceae in livestock using docking based analysis to reveal the classes of antibiotics against which ESBL-producers are active. Rectal swabs from healthy cattle (n=100), goats (n=88), pigs (n=66) were collected from backyard farms in Andaman and Nicober island (India). In total, 304 isolates comprising E.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Biochemistry and Structural Biology, UT Health San Antonio, San Antonio, TX, USA.
SAMHD1 is a dNTPase that impedes replication of HIV-1 in myeloid cells and resting T lymphocytes. Here we elucidate the substrate activation mechanism of SAMHD1, which involves dNTP binding at allosteric sites and transient tetramerization. Our findings reveal that tetramerization alone is insufficient to promote dNTP hydrolysis; instead, the activation mechanism requires an inactive tetrameric intermediate with partially occupied allosteric sites.
View Article and Find Full Text PDFEnviron Sci Technol
January 2025
State Key Laboratory of Heavy Oil Processing, Key Laboratory of Optical Detection Technology for Oil and Gas, College of Science, China University of Petroleum, Beijing 102249, PR China.
The purification efficiency of autoexhaust carbon strongly depends on the heterogeneous interface structure between active metal and oxide, which can modulate the local electronic structure of defect sites to promote the activation of reactant molecules. Herein, the high-dispersion CuO clusters supported on the well-defined CeO nanorods were prepared using the complex deposition slow method. The formation of heteroatomic Cu-O-Ce interfacial structural units as active sites can capture electrons to achieve activation of the NO and O molecules.
View Article and Find Full Text PDFBiochimie
January 2025
Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences, Vavilov street, 32, Moscow, 119991, Russia.
Pyridoxal 5'-phosphate (PLP)-dependent enzymes are involved in many cellular processes and possess unequalled catalytic versatility. Rational design through site-directed mutagenesis is a powerful strategy for creating tailor-made enzymes for a wide range of biocatalytic applications. PLP-dependent methionine γ-lyase (MGL), which degrades sulfur-containing amino acids, is an encouraging enzyme for many therapeutic purposes - from combating bacterial resistant strains and fungi to antitumor activity.
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