Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.4.2.8 (phosphomannomutase)
 238 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

When incubated with their substrates, human phosphomannomutase and L-3-phosphoserine phosphatase are known to form phosphoenzymes with chemical characteristics of an acyl-phosphate. The phosphorylated residue in phosphomannomutase has now been identified by mass spectrometry after reduction of the phosphoenzyme with tritiated borohydride and trypsin digestion. It is the first aspartate in a conserved DVDGT motif. Replacement of either aspartate of this motif by asparagine or glutamate resulted in complete inactivation of the enzyme. The same mutations performed in the DXDST motif of L-3-phosphoserine phosphatase also resulted in complete inactivation of the enzyme, except for the replacement of the second aspartate by glutamate, which reduced the activity by only about 40%. This suggests that the first aspartate of the motif is also the phosphorylated residue in L-3-phosphoserine phosphatase. Data banks contained seven other phosphomutases or phosphatases sharing a similar, totally conserved DXDX(T/V) motif at their amino terminus. One of these (beta-phosphoglucomutase) is shown to form a phosphoenzyme with the characteristics of an acyl-phosphate. In conclusion, phosphomannomutase and L-3-phosphoserine phosphatase belong to a new phosphotransferase family with an amino-terminal DXDX(T/V) motif that serves as an intermediate phosphoryl acceptor.
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PMID:A new class of phosphotransferases phosphorylated on an aspartate residue in an amino-terminal DXDX(T/V) motif. 960 9

Physicians have become accustomed to thinking of certain inborn errors of metabolism (e.g., lysosomal, peroxisomal, and mitochondrial diseases) as being associated with specific subcellular organelles. In recent years, a family of disorders of N-glycosylation has been recognized, in which the metabolic defect is expressed in the cytosol, endoplasmic reticulum, and Golgi apparatus. These could be conveniently thought of as "prelysosomal" disorders. At least six of these entities are characterized by hypoglycosylation of many glycoconjugates, and have been designated as the carbohydrate-deficient glycoprotein syndromes. Given the ubiquity of the products of N-glycosylation in the cellular economy, it is not surprising that these defects in metabolism have protean clinical manifestations. Delayed development and other neurologic symptoms are wedded to variable dysfunctions of the heart, liver, and endocrine and coagulation systems. Patients can have dysmorphic features or cerebellar hypoplasia, attesting to the antenatal expression of these disorders. The most frequently recognized phenotype (several hundred cases worldwide) has been designated carbohydrate-deficient glycoprotein syndrome type la, and results from mutations in phosphomannomutase, a cytosolic enzyme involved in the synthesis of the lipid-linked oligosaccharide that is eventually attached to nascent glycoproteins through the amide group of asparagine residues. All forms of carbohydrate-deficient glycoprotein syndrome express an excess of hypoglycosylated isoforms of circulating transferrin, which serves as a useful screening tool. Physicians should consider screening for carbohydrate-deficient glycoprotein syndrome in individuals with delayed development, seizures, strokelike episodes, cerebellar hypoplasia, and demyelinating neuropathy with or without other signs of multisystem disease.
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PMID:Screening for "prelysosomal disorders": carbohydrate-deficient glycoprotein syndromes. 1059 62

Congenital disorders of glycosylation (CDGs) are a rapidly growing group of inherited disorders caused by defects in the synthesis and processing of the asparagine(ASN)-linked oligosaccharides of glycoproteins. The first CDG patients were described in 1980. Fifteen years later, a phosphomannomutase deficiency was found as the basis of the most frequent type, CDG-Ia. In recent years several novel types have been identified. The N-glycosylation pathway is highly conserved from yeast to human, and the rapid progress in this field can largely be attributed to the systematic application of the knowledge of yeast mutants. Up to now, eight diseases have been characterized, resulting from enzyme or transport defects in the cytosol, endoplasmic reticulum, or Golgi compartment. CDGs affect all organs and particularly the CNS, except for CDG-Ib, which is mainly a hepatic-intestinal disease.
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PMID:Congenital disorders of glycosylation: a review. 1240 4

Many congenital disorders of glycosylation (CDG) can be diagnosed by observing the extent of glycosylation of the abundant serum glycoprotein transferrin (Trf). Trf is an N-glycosylated protein with two asparagine glycation sites. CDG types I are those genetic defects which occur prior to transfer of the complex oligosaccharide to the acceptor asparagine in the cotranslated polypeptide chain. CDG Ia constitutes by far the most frequent form of CDG and is the result of mutations in the phosphomannomutase gene. CDG Ia and the Ib subtype (Phosphomannoisomerase deficiency) result in low cellular mannose-1-phosphate levels, a required precursor for oligosaccharide assembly in the endoplasmic reticulum. The deficiency in oligosaccharides with branched mannose structures is thereafter expressed by the appearance of glycoproteins with unoccupied N-glycosylation sites (hypoglycosylation). Currently, there have been at least 11 Type I defects, type Ia being by far the most frequently occurring. Most, if not all type I defects result in unoccupied N-glycation sites. Hypoglycosylated Trf, also known as carbohydrate-deficient Trf (CDT), can be detected using mass spectrometry (MS) to measure the masses of the serum Trf. The methods for sample preparation using affinity chromatography and MS analysis are described in this unit.
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PMID:Detection of hypo-N-glycosylation using mass spectrometry of transferrin. 1842 10