Publications by authors named "Peter Madzelan"

Article Synopsis
  • Researchers studied the complex formation between chloroacetamide 2,6-diazaadamantane nitroxide radical (ClA-DZD) and cucurbit[7]uril (CB-7), finding a strong association constant in water (1.9 × 10 M) that surpasses previous studies on organic radicals.
  • The encapsulation of ClA-DZD by CB-7 significantly increases its rotational correlation time by 36 times, indicating strong immobilization within the host structure, as confirmed by X-ray crystallography.
  • Upon adding CB-7 to T4 Lysozyme labeled with DZD, improvements in electron spin coherence and interspin distance measurement accuracy were observed, enhancing the potential for advanced DEER measurements near
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Article Synopsis
  • The study investigates the formation of a complex between the chloroacetamide radical (ClA-DZD) and cucurbit[7]uril (CB-7), revealing a strong association constant of 1.9 × 10 M, significantly higher than previously studied radicals.
  • ClA-DZD's rotational mobility is greatly reduced when encapsulated by CB-7, as shown by a 36-fold increase in its rotational correlation time, highlighting the immobilization effect of the host.
  • The addition of CB-7 to a spin-labeled T4 Lysozyme improves measurement sensitivity and measurement accuracy of inter-spin distances, advancing the potential for high-resolution studies in biological environments.
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How changes in enzyme structure and dynamics facilitate passage along the reaction coordinate is a fundamental unanswered question. Here, we use time-resolved mix-and-inject serial crystallography (MISC) at an X-ray free electron laser (XFEL), ambient-temperature X-ray crystallography, computer simulations, and enzyme kinetics to characterize how covalent catalysis modulates isocyanide hydratase (ICH) conformational dynamics throughout its catalytic cycle. We visualize this previously hypothetical reaction mechanism, directly observing formation of a thioimidate covalent intermediate in ICH microcrystals during catalysis.

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Human DJ-1 is a highly conserved and yet functionally enigmatic protein associated with a heritable form of Parkinson's disease. It has been suggested to be a redox-dependent regulatory scaffold, binding to proteins to modulate their function. Here we present the X-ray crystal structure of the orthologue DJ-1 (TgDJ-1) at 2.

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The synthesis of phylloquinone (vitamin K1) in photosynthetic organisms requires a thioesterase that hydrolyzes 1,4-dihydroxy-2-naphthoyl-CoA (DHNA-CoA) to release 1,4-dihydroxy-2-naphthoate (DHNA). Cyanobacteria and plants contain distantly related hotdog-fold thioesterases that catalyze this reaction, although the structural basis of these convergent enzymatic activities is unknown. To investigate this, the crystal structures of hotdog-fold DHNA-CoA thioesterases from the cyanobacterium Synechocystis (Slr0204) and the flowering plant Arabidopsis thaliana (AtDHNAT1) were determined.

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Cysteine residues with depressed pK(a) values are critical for the functions of many proteins. Several types of interactions can stabilize cysteine thiolate anions, including hydrogen bonds between thiol(ate)s and nearby residues as well as electrostatic interactions involving charged residues or dipoles. Dipolar stabilization of thiolates by peptide groups has been suggested to play a particularly important role near the N-termini of α-helices.

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Cystathionine beta-synthase (CBS) plays a central role in homocysteine metabolism, and malfunction of the enzyme leads to homocystinuria, a devastating metabolic disease. CBS contains a pyridoxal 5'-phosphate (PLP) cofactor which catalyzes the synthesis of cystathionine from homocysteine and serine. Mammalian forms of the enzyme also contain a heme group, which is not involved in catalysis.

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In humans, cystathionine beta-synthase (CBS) is a hemeprotein, which catalyzes a pyridoxal phosphate (PLP)-dependent condensation reaction. Changes in the heme environment are communicated to the active site, which is approximately 20A away. In this study, we have examined the role of H67 and R266, which are in the second coordination sphere of the heme ligands, H65 and C52, respectively, in modulating the heme's electronic properties and in transmitting information between the heme and active sites.

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Cystathionine beta-synthase (CBS) catalyzes the condensation of serine and homocysteine to cystathionine, which represents the committing step in the transsulfuration pathway. CBS is unique in being a pyridoxal phosphate-dependent enzyme that has a heme cofactor. The activity of CBS under in vitro conditions is responsive to the redox state of the heme, which is distant from the active site and has been postulated to play a regulatory role.

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Article Synopsis
  • Methionine metabolism produces important compounds like S-adenosylmethionine and glutathione through intermediate homocysteine, which is vital for cancer cell growth.
  • Many cancer cells cannot thrive without methionine, as they show dependence on it instead of its precursor, homocysteine.
  • The study analyzed key enzymes related to homocysteine metabolism in various cancer lines, revealing that lower expression of methionine synthase correlates with slower growth rates in non-small lung cancer cells, and specific prostate cancer cells displayed notable differences in enzyme expression without improving growth despite changes in CBS levels.
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