Adenosine monophosphoramidase activity of Hint and Hnt1 supports function of Kin28, Ccl1, and Tfb3

Pawel Bieganowski; Preston N Garrison; Santosh C Hodawadekar; Gerard Faye; Larry D Barnes; Charles Brenner

doi:10.1074/jbc.M111480200

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Adenosine monophosphoramidase activity of Hint and Hnt1 supports function of Kin28, Ccl1, and Tfb3

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Adenosine monophosphoramidase activity of Hint and Hnt1 supports function of Kin28, Ccl1, and Tfb3

Pawel Bieganowski, Preston N Garrison, Santosh C Hodawadekar, Gerard Faye, Larry D Barnes and Charles Brenner

The Journal of biological chemistry, Vol.277(13), pp.10852-10860

03/29/2002

DOI: 10.1074/jbc.M111480200

PMCID: PMC2556056

PMID: 11805111

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Abstract

The histidine triad superfamily of nucleotide hydrolases and nucleotide transferases consists of a branch of proteins related to Hint and Aprataxin, a branch of Fhit-related hydrolases, and a branch of galactose-1-phosphate uridylyltransferase (GalT)-related transferases. Although substrates of Fhit and GalT are known and consequences of mutations in Aprataxin, Fhit, and GalT are known, good substrates had not been reported for any member of the Hint branch, and mutational consequences were unknown for Hint orthologs, which are the most ancient and widespread proteins in the Hint branch and in the histidine triad superfamily. Here we show that rabbit and yeast Hint hydrolyze the natural product adenosine-5'-monophosphoramidate (AMPNH(2)) in an active-site-dependent manner at second order rates exceeding 1,000,000 m(-1) s(-1). Yeast strains constructed with specific loss of the Hnt1 active site fail to grow on galactose at elevated temperatures. Loss of Hnt1 enzyme activity also leads to hypersensitivity to mutations in Ccl1, Tfb3, and Kin28, which constitute the TFIIK kinase subcomplex of general transcription factor TFIIH and to mutations in Cak1, which phosphorylates Kin28. The target of Hnt1 regulation in this pathway was shown to be downstream of Cak1 and not to affect stability of Kin28 monomers. Functional complementation of all Hnt1 phenotypes was provided by rabbit Hint, which is only 22% identical to yeast Hnt1 but has very similar adenosine monophosphoramidase activity.

Hydrolases - metabolism

Hydrolases - genetics

Phosphorylation

Protein-Serine-Threonine Kinases - genetics

Fungal Proteins - genetics

Transcription Factors - metabolism

Animals

Proteins - metabolism

Mutagenesis

Alleles

Saccharomyces cerevisiae Proteins - metabolism

Plant Proteins

Cyclin-Dependent Kinases

Transcription Factors, TFII

Protein-Serine-Threonine Kinases - metabolism

Fungal Proteins - metabolism

Details

Title: Subtitle: Adenosine monophosphoramidase activity of Hint and Hnt1 supports function of Kin28, Ccl1, and Tfb3
Creators: Pawel Bieganowski - Structural Biology and Bioinformatics Program, Kimmel Cancer Center, Philadelphia, Pennsylvania 19107, USA
Preston N Garrison
Santosh C Hodawadekar
Gerard Faye
Larry D Barnes
Charles Brenner
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.277(13), pp.10852-10860
DOI: 10.1074/jbc.M111480200
PMID: 11805111
PMCID: PMC2556056
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: R01 CA075954-05 / NCI NIH HHS R01 CA075954 / NCI NIH HHS CA75954 / NCI NIH HHS
Language: English
Date published: 03/29/2002
Academic Unit: Biochemistry and Molecular Biology; Internal Medicine
Record Identifier: 9983788431202771

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