Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intrafusal muscle fibres from bull-frog semitendinosus, iliofibularis and sartorius muscles were classified into three types using the histochemical, immunofluorescent and morphological characteristics, with reference to the extrafusal muscle fibres, which were classified into five types in accordance with Rowlerson & Spurway (1988). Immunofluorescent reactions with antibodies against slow or fast myosins obtained from anterior or posterior latissimus dorsi muscles (ALD or PLD), respectively, of chicken were used as the primary criterion. Histochemical profiles of muscle fibres were classified into nine types of myosin ATPase activity as the secondary criterion. Anti-PLD intrafusal fibres (polar zone) with ATPase profiles of moderate to high acid and alkaline stabilities correspond to large nuclear bag fibres in the classification of Diwan & Ito (1989), whereas anti-ALD fibres (polar zone) with alkaline-labile ATPase profiles correspond to medium nuclear bag fibres. On the basis of diameter, anti-PLD fibres (polar zone) with ATPase profiles of moderate to low acid stability and moderate to high alkaline stability seem to correspond to two types of small nuclear chain fibre. Variations between muscles, between intra- and extrafusal fibres and also between zones along intrafusal fibres are discussed.
...
PMID:Classification of the intrafusal muscle fibres in the frog muscle spindle: histochemical and immunofluorescent studies. 214 48

Comparative energetics of chicken latissimus dorsi muscles, tonic anterior (ALD) and phasic posterior (PLD), were investigated by measuring initial heat production. Heat components were analyzed in terms of the equation: E = A + W + alpha(F)(DeltaL) + f(P, t) As the muscles were stretched by increments, heat produced in isometric twitches and tetani decreased in a linear fashion. Two processes are involved: one tension independent, the activation heat, or A; and the other tension dependent, W(i) + alpha(F)(DeltaL) + f(P, t). In twitches, A, per unit tension, is equivalent in the PLD and ALD. Tension-dependent heat, per unit tension, is greater in the PLD due to W(i); but tension-time-related heat, f(P, t), per unit tension, is similar in both muscles. In tetanic contractions, differences in A and f(P, t), per unit tension, are attributed to the greater V(max) in the PLD. The differences in the energetics of isometric contractions in the PLD and ALD, therefore, can be explained by inherent differences in tension development, compliance, and myosin and reticular ATPase activities. Data from isotonic twitches were quantified by means of the equivalent tension technique. Both muscles exhibited an extra heat associated with shortening, alpha(F)(DeltaL). In the PLD, the ratio alpha(F)/P(ot) is greater; it is load independent and (1/2) the value of a/P(o) in both muscles. Enthalpy efficiency, W(e) + W(i)/E, is comparable in both muscles. A Fenn effect is observed only when isotonic energy liberation is compared to a decreasing isometric energy expenditure base line.
...
PMID:Energetics of contraction in phasic and tonic skeletal muscles of the chicken. 473 Jun 69

Myosin has been purified from chicken pectoralis muscle at various stages of development, from 10 days' incubation to approximately 10 months after hatching. Embryonic myosin from the earliest stage showed a high level of ATPase activity, similar to that obtained for adult pectoralis myosin. Two-dimensional peptide mapping of partial chymotryptic digests showed, however, that is heavy chain is quite different from that of adult fast myosin. The immunological crossreactivity observed between embryonic myosin and adult fast (pectoralis) myosin is therefore due to shared antigenic determinants rather than the presence of any adult isoforms. In an accompanying paper we will show that embryonic myosin at 10 days' incubation is not a single species, but consists of at least two heavy chain isozymes. The minor fraction binds slow light chains preferentially, and appears to be largely responsible for the observed crossreactivity with slow (ALD) myosin. None of the embryonic myosins is equivalent to the adult forms. Prior to hatching, LC3f is present only in very small amounts (less than 5%), and the adult light chain pattern, containing LC1f and LC3f in equimolar amounts, is not generated until after one week post-hatching. At about that time a new heavy chain population is detected, different from either the embryonic heavy chain or the adult heavy chain. The adult heavy chain peptide pattern appears from about three weeks' post-hatching, but a map indistinguishable from that of adult myosin is not observed until about 26 weeks. None of the observed differences in peptide maps can be related to different strains of chicken; pectoralis myosin from adult White Rock gave an identical map to that from White Leghorn. Unexpectedly, posterior latissimus dorsi (PLD) myosin from White Leghorn appears to be different from pectoralis myosin from the same strain, despite the histochemical and immunocytochemical similarity of the two muscles. We conclude that myosin polymorphism is widespread in muscle tissue, and that the expression of myosin isozymes and their subunits is under developmental regulation.
...
PMID:Myosin isozymes in avian skeletal muscles. I. Sequential expression of myosin isozymes in developing chicken pectoralis muscles. 623 Mar 70

Adrenoleukodystrophy (X-ALD) is a demyelinating disorder characterized by the accumulation of saturated very-long-chain fatty acids (> C22:0) due to the impaired activity of lignoceroyl-CoA ligase. The gene responsible for the disease was found to code for a 84-kDa peroxisomal integral membrane protein. Its amino acid sequence has high homology with the ATP-binding cassette superfamily of transporters and it is predicted to have six membrane-spanning segments and a putative ATP-binding domain. To define the function of ALDP, we studied the topology of its ATP-binding domain by using antibodies (1D6) against a hydrophobic domain (amino acid residues 279 to 482) and antibodies (Abct) against the C-terminal 15-amino-acid hydrophilic domain (amino acid residues 731 to 745) of ALDP. The observation of punctate fluorescence in permeabilized ALD fibroblasts, using Abct antibodies but not with antibodies against catalase, suggests that the C-terminal segment of ALDP is projected toward the cytoplasm from the peroxisomal membrane. Trypsinization of intact peroxisomes under isotonic conditions abolishes the Abct antibody recognition site, whereas the 1D6 antibodies identify a degradation product of 43-kDa protein that has been protected and retained by the membrane. This again suggests that the C-terminal portion of the ALDP protein is located on the outside (cytoplasmic) face of the peroxisomal membrane. Additional support for this conclusion was obtained by purification of the ALDP C-terminal domain, released from purified rat liver peroxisomes incubated with the cytosolic fraction, using blue-Sepharose affinity chromatography. A 47-kDa peptide retained by the column was recognized by Western blot analysis with Abct antibodies against the C-terminal sequence of ALDP and this polypeptide on polyvinylidene difluoride membrane was able to bind [gamma-32P]ATP in vitro in the presence of Mg2+. These results demonstrate that the C-terminal peptide containing the ATP-binding domains of ALDP is on the cytoplasmic surface of the peroxisomal membrane where this domain may function as an ATPase to support the functional role of ALDP in the peroxisomal membrane.
...
PMID:Topology of ATP-binding domain of adrenoleukodystrophy gene product in peroxisomes. 890 Apr 13

The peroxisome biogenesis disorders (PBDs), including Zellweger syndrome (ZS) and neonatal adrenoleukodystrophy (NALD), are autosomal recessive diseases caused by defects in peroxisome assembly, for which at least 10 complementation groups have been reported. We have isolated a human PEX1 cDNA (HsPEX1) by functional complementation of peroxisome deficiency of a mutant Chinese hamster ovary (CHO) cell line, ZP107, transformed with peroxisome targeting signal type 1-tagged "enhanced" green fluorescent protein. This cDNA encodes a hydrophilic protein (Pex1p) comprising 1,283 amino acids, with high homology to the AAA-type ATPase family. A stable transformant of ZP107 with HsPEX1 was morphologically and biochemically restored for peroxisome biogenesis. HsPEX1 expression restored peroxisomal protein import in fibroblasts from three patients with ZS and NALD of complementation group I (CG-I), which is the highest-incidence PBD. A CG-I ZS patient (PBDE-04) possessed compound heterozygous, inactivating mutations: a missense point mutation resulting in Leu-664 --> Pro and a deletion of the sequence from Gly-634 to His-690 presumably caused by missplicing (splice site mutation). Both PBDE-04 PEX1 cDNAs were defective in peroxisome-restoring activity when expressed in the patient fibroblasts as well as in ZP107 cells. These results demonstrate that PEX1 is the causative gene for CG-I peroxisomal disorders.
...
PMID:Human PEX1 cloned by functional complementation on a CHO cell mutant is responsible for peroxisome-deficient Zellweger syndrome of complementation group I. 953 40

The peroxisome biogenesis disorders (PBDs), including Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), are autosomal recessive diseases caused by deficiency of peroxisome assembly as well as malfunction of peroxisomes, where >10 genotypes have been reported. ZS patients manifest the most severe clinical and biochemical abnormalities, while those with NALD and IRD show the least severity and the mildest features, respectively. PEX1 is the causative gene for PBDs of complementation group I (CG1), the highest incidence PBD, and encodes the peroxin, Pex1p, a member of the AAA ATPase family. In the present work, we found that peroxisomes were morphologically and biochemically formed at 30 but not 37 degrees C, in the fibroblasts from all CG1 IRD patients examined, whereas almost no peroxisomes were seen in ZS and NALD cells, even at 30 degrees C. A point missense mutation, G843D, was identified in the PEX1 allele of most CG1 IRD patients. The mutant PEX1, termed HsPEX1G843D, gave rise to the same temperature-sensitive phenotype on CG1 CHO cell mutants upon transfection. Collectively, these results demonstrate temperature-sensitive peroxisome assembly to be responsible for the mildness of the clinical features of PEX1 -defective IRD of CG1.
...
PMID:Temperature-sensitive mutation in PEX1 moderates the phenotypes of peroxisome deficiency disorders. 981 26

Peroxisome biogenesis disorders are a heterogeneous group of human neurodegenerative diseases caused by peroxisomal metabolic dysfunction. At the molecular level, these disorders arise from mutations in PEX genes that encode proteins required for the import of proteins into the peroxisomal lumen. The Zellweger syndrome spectrum of diseases is a major sub-set of these disorders and represents a clinical continuum from Zellweger syndrome (the most severe) through neonatal adrenoleukodystrophy to infantile Refsum disease. The PEX1 gene, which encodes a cytoplasmic AAA ATPase, is the responsible gene in more than half of the Zellweger syndrome spectrum patients, and mutations in PEX1 can account for the full spectrum of phenotypes seen in these patients. In these studies, we have undertaken mutation analysis of PEX1 in skin fibroblast cell lines from Australasian Zellweger syndrome spectrum patients. A previously reported common PEX1 mutation that gives rise to a G843D substitution and correlates with the less severe disease phenotypes has been found to be present at high frequency in our patient cohort. We also report a novel PEX1 mutation that occurs at high frequency in Zellweger syndrome spectrum patients. This mutation produces a frameshift in exon 13, a change that leads to the premature truncation of the PEX1 protein. A Zellweger syndrome patient who was homozygous for this mutation and who survived for less than two months from birth had undetectable levels of PEX1 mRNA. This new common mutation therefore correlates with a severe disease phenotype. We have adopted procedures for the detection of this mutation for successful prenatal diagnosis.
...
PMID:A common PEX1 frameshift mutation in patients with disorders of peroxisome biogenesis correlates with the severe Zellweger syndrome phenotype. 1048 Mar 53

The 70-kDa peroxisomal membrane protein (PMP70) and the adrenoleukodystrophy protein (ALDP) are half ATP binding cassette (ABC) transporters in the peroxisome membrane. Mutations in the ALD gene encoding ALDP result in the X-linked neurodegenerative disorder adrenoleukodystrophy. Plausible models exist to show a role for ATP hydrolysis in peroxisomal ABC transporter functions. Here, we describe the first measurements of the rate of ATP binding and hydrolysis by purified nucleotide binding fold (NBF) fusion proteins of PMP70 and ALDP. Both proteins act as an ATP specific binding subunit releasing ADP after ATP hydrolysis; they did not exhibit GTPase activity. Mutations in conserved residues of the nucleotidases (PMP70: G478R, S572I; ALDP: G512S, S606L) altered ATPase activity. Furthermore, our results indicate that these mutations do not influence homodimerization or heterodimerization of ALDP or PMP70. The study provides evidence that peroxisomal ABC transporters utilize ATP to become a functional transporter.
...
PMID:Characterization and functional analysis of the nucleotide binding fold in human peroxisomal ATP binding cassette transporters. 1124 39

The peroxisome biogenesis disorders (PBDs) are a group of neuronal migration/neurodegenerative disorders that arise from defects in PEX genes. A major subgroup of the PBDs includes Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD), and infantile Refsum disease (IRD). These three disorders represent a clinical continuum with Zellweger syndrome the most severe. Mutations in the PEX1 gene, which encodes a protein of the AAA ATPase family involved in peroxisome matrix protein import, account for the genetic defect in more than half of the patients in this PBD subgroup. We report here on the results of PEX1 mutation detection in an Australasian cohort of PEX1-deficient PBD patients. This screen has identified five novel mutations, including nonsense mutations in exons 14 and 19 and single nucleotide deletions in exons 5 and 18. Significantly, the allele carrying the exon 18 frameshift mutation is present at moderately high frequency (approx. 10%) in this patient cohort. The fifth mutation is a missense mutation (R798G) that attenuates, but does not abolish PEX1 function. We have evaluated the cellular impact of these novel mutations, along with that of the two most common PEX1 mutations (c.2097-2098insT and G843D), in PBD patients by determining the levels of PEX1 mRNA, PEX1 protein, and peroxisome protein import. The findings are consistent with a close correlation between cellular phenotype, disease severity, and PEX1 genotype.
...
PMID:Novel PEX1 mutations and genotype-phenotype correlations in Australasian peroxisome biogenesis disorder patients. 1240 31

X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder characterized by abnormal accumulation of saturated very long chain fatty acids in tissues and body fluids with predominance in brain white matter and adrenal cortex. The clinical phenotype is highly variable ranging from the severe childhood cerebral form to asymptomatic persons. The responsible ALD gene encodes the adrenoleukodystrophy protein (ALDP), a peroxisomal integral membrane protein that is a member of the ATP-binding cassette (ABC) transporter protein family. The patient gene mutations are heterogeneously distributed over the functional domains of ALDP. The extreme variability in clinical phenotype, even within one affected family, indicates that besides the ALD gene mutations other factors strongly influence the clinical phenotype. To understand the cell biology and function of mammalian peroxisomal ABC transporters and to determine their role in the pathogenesis of X-ALD we developed a system for expressing functional ABC protein domains in fusion with the maltose binding protein. Wild type and mutant fusion proteins of the nucleotide-binding fold were overexpressed, purified, and characterized by photoaffinity labeling with 8-azido ATP or 8-azido GTP and a coupled ATP regenerating enzyme assay for ATPase activity. Our studies provide evidence that peroxisomal ABC transporters utilize ATP to become a functional transporter and that ALD gene mutations alter peroxisomal transport function. The established disease model will be used further to study the influence of possible disease modifier proteins on ALDP function.
...
PMID:Functional characterization of the adrenoleukodystrophy protein (ALDP) and disease pathogenesis. 1253 Jun 90


1 2 Next >>

---