Functional analysis of YTH-like domain of novel protein BC1
Date Issued
2004
Date
2004
Author(s)
Hsiao-Yuan, Kao
DOI
en-US
Abstract
Hereditary progressive dystonia (HPD) or Dopa-repsonsive dystonia (DRD) is a heredity form of dystonia caused by mutation in GTP cyclohydrolase I (GCH) gene, which is responsive for the first and rate limiting enzyme of tetrahydrobiopterin (BH4) synthesis. GCH mutations cause a reduction in BH4 and consequently in low TH tyrosine hydrolase, which diminished dopamine production that leads to symptoms of dopamine deficiency. GCH activity of DRD patients in brain is only 20% of normal value regardless of the presence of active allele suggesting a dominant negative effect.
While establishing a HeLa cell lines showing DN effect of GCH mutation, we accidentally screened a line of HeLa that did not have the DN phenomenon. Through PCR selected cDNA subtraction method, we found many well studied genes such as Hsp70 along with novel gene BC1 (named after Institute of Biological Chemistry) are distinctly and highly expressed in non-DN cells. Blast search of the non-redundant NCBI database with the complete BC1 amino acid sequence detected a conserve YTH-like domain located at the C-terminal stretch (437-526aa) of BC1.
In this study, we discovered that purified recombinant YTH domain of BC1 appears to be functional. YTH possesses ATP binding ability and a maximum specific ATPase activity of 0.52 nmole Pi released per min per mg at 45°C. Since BC1 doesn’t contain traditional ATP binding domain such as Walker A, Walker B, P loop motif, more evidence are required to prove BC1 as a novel ATPase.
Subjects
ATP-結合
BC1
GTP cyclohydrolase I
ATP水解
遺傳性漸進式肌緊張力不足
Hereditary progressive Dystonia
GTP cyclohydrolas
Type
other
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