ArticlePhysiological genomics2004
Altered specificity of Hint-W123Q supports a role for Hint inhibition by ASW in avian sex determination.
Article in Physiological genomics, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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Who cites it
7 citing papers in PubMed, 26 citations in OpenAlex.
- Expression, purification, crystallization and preliminary X-ray crystallographic analysis of human histidine triad nucleotide-binding protein 2 (hHINT2).Acta crystallographica. Section F, Structural biology and crystallization communications · 2013Article
- Kinetic mechanism of human histidine triad nucleotide binding protein 1.Biochemistry · 2013Article
- Loss-of-function mutations in HINT1 cause axonal neuropathy with neuromyotonia.Nature genetics · 2012Article
- A new crystal form of human histidine triad nucleotide-binding protein 1 (hHINT1) in complex with adenosine 5'-monophosphate at 1.38 Å resolution.Acta crystallographica. Section F, Structural biology and crystallization communications · 2012Article
- Side chain independent recognition of aminoacyl adenylates by the Hint1 transcription suppressor.The journal of physical chemistry. B · 2012Article
- Hint2, a mitochondrial apoptotic sensitizer down-regulated in hepatocellular carcinoma.Gastroenterology · 2006Article
- Disease-associated mutations inactivate AMP-lysine hydrolase activity of Aprataxin.The Journal of biological chemistry · 2005Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Hint is a universally conserved, dimeric AMP-lysine hydrolase encoded on the avian Z chromosome. Tandemly repeated on the female-specific W chromosome, Asw encodes a potentially sex-determining, dominant-negative Hint dimerization partner whose substrate-interacting residues were specifically altered in evolution. To test the hypothesis that Gln127 of Asw is responsible for depression and/or alteration of Hint enzyme activity, a corresponding mutant was created in the chicken Hint homodimer, and a novel substrate was developed that links reversal of AMP-lysine modification to aminomethylcoumarin release. Strikingly, the Hint-W123Q substitution reduced k(cat)/K(m) for AMP-lysine hydrolysis 17-fold, while it increased specificity for AMP-para-nitroaniline hydrolysis by 160-fold. The resulting 2,700-fold switch in enzyme specificity suggests that Gln127 could be the dominant component of Asw dominant negativity in avian feminization.
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