A new crystal form of human histidine triad nucleotide-binding protein 1 (hHINT1) in complex with adenosine 5′-monophosphate at 1.38 Å resolution

Dolot, Rafał; Ozga, M.; Włodarczyk, Artur; Krakowiak, Agnieszka; Nawrot, Barbara

doi:10.1107/s1744309112029491

Cited by 13 publications

(20 citation statements)

References 54 publications

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“…Compared to the structure of AMP (pdb: 3TW2), 25 an additional hydrogen bond between the carbonyl of the acyl-sulfamate of 7 and active site Ser107 was observed. Interestingly, this interaction was not found in the structure with Bio-AMS (Supplementary Table 2).…”

Section: Acs Medicinal Chemistry Lettersmentioning

confidence: 99%

Design, Synthesis, and Characterization of Sulfamide and Sulfamate Nucleotidomimetic Inhibitors of hHint1

Shah

Strom

Zhou

et al. 2016

ACS Med. Chem. Lett.

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Hint1 has recently emerged to be an important target of interest due to its involvement in the regulation of a broad range of CNS functions including opioid signaling, tolerance, neuropathic pain, and nicotine dependence. A series of inhibitors were rationally designed, synthesized, and tested for their inhibitory activity against hHint1 using isothermal titration calorimetry (ITC). The studies resulted in the development of the first small-molecule inhibitors of hHint1 with submicromolar binding affinities. A combination of thermodynamic and high-resolution X-ray crystallographic studies provides an insight into the biomolecular recognition of ligands by hHint1. These novel inhibitors have potential utility as molecular probes to better understand the role and function of hHint1 in the CNS.

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Section: Acs Medicinal Chemistry Lettersmentioning

confidence: 99%

Design, Synthesis, and Characterization of Sulfamide and Sulfamate Nucleotidomimetic Inhibitors of hHint1

Shah

Strom

Zhou

et al. 2016

ACS Med. Chem. Lett.

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“…Overall, the human and yeast APTX HIT domains resemble other HIT superfamily nucleotide hydrolases including FHIT, PKCI (Lima et al, 1997a; Lima et al, 1997b), Hint1 (Dolot et al, 2012) and Hint2 (Maize et al, 2013). This canonical HIT architecture is typified by a central five-stranded anti-parallel β-sheet encircled by a number of helical elements on three sides of the sheet (Fig.…”

Section: The Aptx Hit-znf Catalytic Corementioning

confidence: 99%

Molecular underpinnings of Aprataxin RNA/DNA deadenylase function and dysfunction in neurological disease

Schellenberg

Tumbale

Williams

2015

Progress in Biophysics and Molecular Biology

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Eukaryotic DNA ligases seal DNA breaks in the final step of DNA replication and repair transactions via a three-step reaction mechanism that can abort if DNA ligases encounter modified DNA termini, such as the products and repair intermediates of DNA oxidation, alkylation, or the aberrant incorporation of ribonucleotides into genomic DNA. Such abortive DNA ligation reactions create 5’–adenylated nucleic acid termini in the context of DNA and RNA-DNA substrates in DNA base excision repair (BER), double strand break repair (DSBR) and ribonucleotide excision repair (RER). Aprataxin (APTX), a protein altered in the heritable neurological disorder Ataxia with Oculomotor Apraxia 1 (AOA1), acts as a DNA ligase “proofreader” to directly reverse AMP-modified nucleic acid termini in DNA- and RNA-DNA damage responses. Herein, we survey APTX function and the emerging cell biological, structural and biochemical data that has established a molecular foundation for understanding the APTX mediated deadenylation reaction, and is providing insights into the molecular bases of APTX deficiency in AOA1.

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“…8A) is based on a top-ranked Mycobacterium paratuberculosis HIT-like protein structure (PDB 3P0T) (24) with a global model quality estimate (GMQE) quality score of 0.68, indicative of good reliability and accuracy. To reveal the potential interactions in the substrate-binding pocket, the model structure of MccH Hmi was superimposed with the crystal structure of the human histidine-triad nucleotide-binding protein 1 (hHINT1) in complex with AMP (PDB 3TW2) (25).…”

Section: Structural Model Of Mcch Hmi the Loss Of Functional Activimentioning

confidence: 99%

Histidine-Triad Hydrolases Provide Resistance to Peptide-Nucleotide Antibiotics

Yagmurov

Tsibulskaya

Livenskyi

et al. 2020

mBio

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The Escherichia coli microcin C (McC) and related compounds are potent Trojan horse peptide-nucleotide antibiotics. The peptide part facilitates transport into sensitive cells. Inside the cell, the peptide part is degraded by nonspecific peptidases releasing an aspartamide-adenylate containing a phosphoramide bond. This nonhydrolyzable compound inhibits aspartyl-tRNA synthetase. In addition to the efficient export of McC outside the producing cells, special mechanisms have evolved to avoid self-toxicity caused by the degradation of the peptide part inside the producers. Here, we report that histidine-triad (HIT) hydrolases encoded in biosynthetic clusters of some McC homologs or by standalone genes confer resistance to McC-like compounds by hydrolyzing the phosphoramide bond in toxic aspartamide-adenosine, rendering them inactive. IMPORTANCE Uncovering the mechanisms of resistance is a required step for countering the looming antibiotic resistance crisis. In this communication, we show how universally conserved histidine-triad hydrolases provide resistance to microcin C, a potent inhibitor of bacterial protein synthesis.

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A new crystal form of human histidine triad nucleotide-binding protein 1 (hHINT1) in complex with adenosine 5′-monophosphate at 1.38 Å resolution

Cited by 13 publications

References 54 publications

Design, Synthesis, and Characterization of Sulfamide and Sulfamate Nucleotidomimetic Inhibitors of hHint1

Design, Synthesis, and Characterization of Sulfamide and Sulfamate Nucleotidomimetic Inhibitors of hHint1

Molecular underpinnings of Aprataxin RNA/DNA deadenylase function and dysfunction in neurological disease

Histidine-Triad Hydrolases Provide Resistance to Peptide-Nucleotide Antibiotics

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