Subcellular Localization of Galactose-1-phosphate Uridylyltransferase in the Yeast Saccharomyces cerevisiae

Christacos, Nicole C.; Marson, Melanie J.; Wells, Lance; Riehman, Kristen; Fridovich‐Keil, Judith L.

doi:10.1006/mgme.2000.3019

Cited by 27 publications

(21 citation statements)

References 16 publications

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“…The GALT enzyme (Gal7p) localizes to discrete spots within the cytoplasm and this localization is dependent upon the presence of Gal10p and the galactokinase (Gal1p) (34). Although human GALT expressed in yeast does localise to spots (34), there is as yet no biochemical evidence for the direct physical association of the human Leloir pathway enzymes. Indeed residues in Gal10p which provide contacts between the GALE-and GALM-like domains are not well conserved in the human proteins (17).…”

Section: Structural Correlations Of Disease-causing Mutantsmentioning

confidence: 99%

The structural and molecular biology of type III galactosemia

Timson¹

2006

IUBMB Life (International Union of Biochemistry and Molecular B

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SummaryType III galactosemia is a genetic disease caused by mutations in the gene encoding UDP-galactose 4-epimerase. A variety of different point mutations located throughout the gene can be responsible. The main, disease-causing effects of these mutations appear to be a reduction in the catalytic rate constant (k cat ) and an increase in the proteolytic sensitivity of the protein. Many of the mutations are distant from the active site of the enzyme and therefore must be assumed to affect the overall fold of the protein.Although the disease was previously classified into a severe, or generalized, form and an essentially benign, or peripheral, form this distinction has been blurred by recent work. Instead of two separate conditions it now appears that type III galactosemia is a continuum and that the symptoms will vary depending on the mutation(s) carried by the individual sufferer. This new way of looking at the disease has implications for the treatment and long term monitoring of patients. IUBMB Life, 58: 83 -89, 2006 Keywords Leloir pathway; UDP-galactose 4-epimerase; GALE; genetic disease; galactose; short-chain dehydrogenase/ reductase.Abbreviations GALM, Galactose mutarotase; GALK1, galactokinase; GALT, galactose-1-phosphate uridyltransferase; GALE, UDP-galactose 4-epimerase; SDR, the short-chain dehydrogenase/reductase; k cat , the catalytic rate constant or turnover number; K m , the Michaelis constant.

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Section: Structural Correlations Of Disease-causing Mutantsmentioning

confidence: 99%

The structural and molecular biology of type III galactosemia

Timson¹

2006

IUBMB Life (International Union of Biochemistry and Molecular B

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“…Christacos et al [55] have suggested substrate/product channeling or other interactions that could alter the kinetics of the enzymes, based on the experimental evidence of gal7p subcellular localization, which is dependent upon coexpression of gal1p and gal10p; 4)…”

Section: Udp-galactose 4-epimerasementioning

confidence: 99%

Evolution of design principles in biochemical networks

et al. 2004

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Computer modelling and simulation are commonly used to analyse engineered systems.Biological systems differ in that they often can not be accurately characterized, so simulations are far from exact. Nonetheless , we argue in this paper that evolution results in recurring, dynamic organizational principles in biological systems, and that simulation can help to identify them and analyse their dynamic properties. As a specific example, we present a dynamic model of the galactose utilization pathway in yeast, and highlight several features of the model that embody such "design principles".

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“…This discrete localization was abolished in yeast strains in which the galactokinase or UDP-galactose 4 0 -epimerase genes had been deleted. This suggested that the localization of Gal7p was determined by the other enzymes, consistent with the formation of discrete, multienzyme complexes (49). Interestingly, when the human GALT gene was substituted for the yeast one, similar localization was observed (49).…”

Section: Future Perspectivesmentioning

confidence: 76%

“…This suggested that the localization of Gal7p was determined by the other enzymes, consistent with the formation of discrete, multienzyme complexes (49). Interestingly, when the human GALT gene was substituted for the yeast one, similar localization was observed (49). To date, no localization studies have been carried out on the Leloir pathway enzymes in human cells.…”

Section: Future Perspectivesmentioning

confidence: 86%

Structural and molecular biology of type I galactosemia: Disease‐associated mutations

McCorvie

Timson

2011

IUBMB Life

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SummaryType I galactosemia results from reduced galactose 1-phosphate uridylyltransferase (GALT) activity. Signs of disease include damage to the eyes, brain, liver, and ovaries. However, the exact nature and severity of the pathology depends on the mutation(s) in the patient's genes and his/her environment. Considerable enzymological and structural knowledge has been accumulated and this provides a basis to explain, at a biochemical level, impairment in the enzyme in the more than 230 disease-associated variants, which have been described. The most common variant, Q188R, occurs close to the active site and the dimer interface. The substitution probably disrupts both UDPsugar binding and homodimer stability. Other alterations, for example K285N, occur close to the surface of the enzyme and most likely affect the folding and stability of the enzyme. There are a number of unanswered questions in the field, which require resolution. These include the possibility that the main enzymes of galactose metabolism form a supramolecular complex and the need for a high resolution crystal structure of human GALT.2011 IUBMB IUBMB Life, 63(11): 949-954, 2011 Keywords galactose metabolism; disease-associated mutation;GALT; galactose 1-phosphate uridylyltransferase; histidine triad transferase; UMP-histidine.Abbreviations GALT, galactose 1-phosphate uridylyltransferase; GALE, activities of GALT and UDP-galactose 40-epimerase.

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Subcellular Localization of Galactose-1-phosphate Uridylyltransferase in the Yeast Saccharomyces cerevisiae

Cited by 27 publications

References 16 publications

The structural and molecular biology of type III galactosemia

The structural and molecular biology of type III galactosemia

Evolution of design principles in biochemical networks

Structural and molecular biology of type I galactosemia: Disease‐associated mutations

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