Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.2.1.22 (cystathionine beta-synthase)
 965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have screened a rat brain library to identify proteins which interact with the 5'-end of huntingtin (amino acids 1-171), including the polyglutamine tract, in the yeast two-hybrid system. We detected an interaction with cystathionine beta-synthase (CBS) [L-serine hydrolyase (adding homocysteine), EC 4.2.1.22], which was confirmed in vitro using His-tagged CBS expressed in Escherichia coli , which was able to specifically bind both rat and human full-length huntingtin. Neither normal nor expanded polyglutamine repeat alone interacted with CBS in the yeast two-hybrid system and nor did constructs containing SBMA or DRPLA with normal or expanded polyglutamine tracts. CBS therefore appears to bind specifically to huntingtin. CBS deficiency is associated with homocystinuria, which is known to affect various physiological systems, including the central nervous system. Homocysteine, one of the substrates of CBS, is known to accumulate in homocystinuria and is metabolized to homocysteate and homocysteine sulphinate, both known to be powerful excitotoxic amino acids. It has been suggested that Huntington's disease involves the action of excitotoxic amino acids and this interaction with CBS may suggest a mechanism for such excitotoxic damage.
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PMID:Huntingtin interacts with cystathionine beta-synthase. 946 92

The recent knowledges about the functions of huntingtin and the pathomechanism of Huntington disease are reviewed. Several binding proteins such as HAP1, ubiquitin-conjugating enzyme, HIP1, glyceraldehyde-3-phosphate-dehydrogenase(GAPDH), and cystathionine beta-synthase are identified. One of the functions of huntingtin suggested by those binding proteins is organella transport. In addition huntington binds with WW domain proteins and SH3 domain. The most exciting discovery of Huntington disease pathomechanism is identification of nuclear inclusions in transgenic mouse model of Huntington disease. The discussion about the significance of nuclear inclusion for the cell death was reviewed.
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PMID:[The function of Huntington disease gene product (huntingtin) and the pathomechanism of Huntington disease]. 1022 88

Huntingtin was localized by using a series of antibodies that detected different areas of the protein from the immediate N-terminus to the C-terminal region of the protein. The more C-terminal antibodies gave a cytoplasmic localization in neurons of the brain in controls and cases of Huntington's disease (HD). The N-terminal antibody, however, gave a distinctive pattern of immunoreactivity in the HD brain, with marked staining of axon tracts and white matter and the detection of densely staining intranuclear inclusions. This implies some processing differences between mutated and normal huntingtin. We have also localized two interacting proteins, cystathionine beta-synthase and the nuclear receptor co-repressor (N-CoR), in brain. Cystathionine beta-synthase was not relocalized in HD brain, but the N-CoR was excluded from neuronal nuclei in HD brain, and a further protein that exists in the same repression complex, mSin3, was similarly excluded. We conclude that the co-repressor might have a part in HD pathology.
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PMID:The localization and interactions of huntingtin. 1043 1