Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent pharmacological and functional studies have suggested the presence of more than one alpha-1 adrenergic receptor subtype in human corpus cavernosum (HCC). In this study, we sought to identify the alpha-1 adrenergic receptor (alpha 1-AR) subtypes expressed in HCC whole tissue and in trabecular smooth muscle subcultured from this tissue. We have utilized RNase protection assays and in situ hybridization (ISH) techniques to identify and localize these receptor subtypes. RNase protection assays of mRNA isolated from whole tissue demonstrated the presence of mRNA transcripts for three alpha 1-AR receptor subtypes (alpha 1d, alpha 1b, and alpha 1a). alpha 1d-AR and alpha 1a-AR appear to be more abundant than alpha 1b-AR. The identification and localization of mRNA for alpha 1-AR subtypes in whole tissue was demonstrated by RNA protection assays and ISH analysis. Immunocytochemical analysis of alpha 1-AR by an antipeptide antibody developed against a specific amino acid sequence derived from alpha 1d-AR subtype demonstrated specific staining of the smooth muscle cells, suggesting the expression of alpha 1d-AR subtype. In cultured HCC smooth muscle cells (HCC SMC), phenylephrine,alpha 1-AR agonist stimulated Na+/K+ ATPase activity, suggesting the presence of functional alpha 1-AR. RNase protection assay of mRNA isolated from HCC SMC grown in culture further demonstrated the presence of mRNA transcripts for alpha 1d-AR and alpha 1a-AR subtypes. ISH analysis and confocal microscopy also indicate that the SMC express the alpha 1d-AR and alpha 1a-AR subtypes. The data presented suggests that HCC and SMC derived from this tissue express at least three alpha 1-AR subtypes. Identification of these receptor subtypes should allow characterization of the functional role of these receptor subtypes in regulation of trabecular smooth muscle tone and penile detumescence.
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PMID:Identification of alpha 1-adrenergic receptor subtypes in human corpus cavernosum tissue and in cultured trabecular smooth muscle cells. 872 94

13S condensin is a five-subunit protein complex that plays a central role in mitotic chromosome condensation in Xenopus egg extracts. Two core subunits of this complex, XCAP-C and XCAP-E, belong to an emerging family of putative ATPases, the SMC family. We report here that 13S condensin has a DNA-stimulated ATPase activity and exhibits a high affinity for structured DNAs such as cruciform DNA. 13S condensin is able to introduce positive supercoils into a closed circular DNA in the presence of bacterial or eukaryotic topoisomerase I. The supercoiling reaction is ATP-dependent. We propose that 13S condensin wraps DNA in a right-handed direction by utilizing the energy of ATP hydrolysis. This reaction may represent a key mechanism underlying the compaction of chromatin fibers during mitosis.
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PMID:ATP-dependent positive supercoiling of DNA by 13S condensin: a biochemical implication for chromosome condensation. 928 43

SMC (structural maintenance of chromosomes) proteins are putative ATPases that are highly conserved among Bacteria, Archaea and Eucarya. Eukaryotic SMC proteins are implicated in a diverse range of chromosome dynamics including chromosome condensation, dosage compensation and recombinational repair. In eukaryotes, two different SMC proteins form a heterodimer, which in turn acts as the core component of a large protein complex. Despite recent progress, no ATP-dependent activity has been found in individual SMC subunits. We report here the first biochemical characterization of a bacterial SMC protein from Bacillus subtilis. Unlike eukaryotic versions, the B.subtilis SMC protein (BsSMC) is a simple homodimer with no associated subunits. It binds preferentially to single-stranded DNA (ssDNA) and has a ssDNA-stimulated ATPase activity. In the presence of ATP, BsSMC forms large nucleoprotein aggregates in a ssDNA-specific manner. Proteolytic cleavage of BsSMC is changed upon binding to ATP and ssDNA. The energy-dependent aggregation of ssDNA might represent a primitive type of chromosome condensation that occurs during segregation of bacterial chromosomes.
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PMID:ATP-dependent aggregation of single-stranded DNA by a bacterial SMC homodimer. 984 17

The study of higher order chromosome structure and how it is modified through the course of the cell cycle has fascinated geneticists, biochemists, and cell biologists for decades. The results from many diverse technical avenues have converged in the discovery of a large superfamily of chromosome-associated proteins known as SMCs, for structural maintenance of chromosomes, which are predicted to have ATPase activity. Now found in all eukaryotes examined, and numerous prokaryotes as well, SMCs play crucial roles in chromatid cohesion, chromosome condensation, sex chromosome dosage compensation, and DNA recombination repair. In eukaryotes, SMCs exist in five subfamilies, which appear to associate with one another in particular pairs to perform their specific functions. In this review, we summarize current progress examining the roles these proteins, and the complexes they form, play in chromosome metabolism. We also present a twist in the SMC story, with the possibility of one SMC moonlighting in an unpredicted location.
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PMID:Review: SMCs in the world of chromosome biology- from prokaryotes to higher eukaryotes. 1080 64

To clarify the key role of Rad50 in DNA double-strand break repair (DSBR), we biochemically and structurally characterized ATP-bound and ATP-free Rad50 catalytic domain (Rad50cd) from Pyrococcus furiosus. Rad50cd displays ATPase activity plus ATP-controlled dimerization and DNA binding activities. Rad50cd crystal structures identify probable protein and DNA interfaces and reveal an ABC-ATPase fold, linking Rad50 molecular mechanisms to ABC transporters, including P glycoprotein and cystic fibrosis transmembrane conductance regulator. Binding of ATP gamma-phosphates to conserved signature motifs in two opposing Rad50cd molecules promotes dimerization that likely couples ATP hydrolysis to dimer dissociation and DNA release. These results, validated by mutations, suggest unified molecular mechanisms for ATP-driven cooperativity and allosteric control of ABC-ATPases in DSBR, membrane transport, and chromosome condensation by SMC proteins.
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PMID:Structural biology of Rad50 ATPase: ATP-driven conformational control in DNA double-strand break repair and the ABC-ATPase superfamily. 1089 49

SMC (structural maintenance of chromosomes) proteins are large coiled-coil proteins involved in chromosome condensation, sister chromatid cohesion, and DNA double-strand break processing. They share a conserved five-domain architecture with three globular domains separated by two long coiled-coil segments. The coiled-coil segments are antiparallel, bringing the N and C-terminal globular domains together. We have expressed a fusion protein of the N and C-terminal globular domains of Thermotoga maritima SMC in Escherichia coli by replacing the approximately 900 residue coiled-coil and hinge segment with a short peptide linker. The SMC head domain (SMChd) binds and condenses DNA in an ATP-dependent manner. Using selenomethionine-substituted protein and multiple anomalous dispersion phasing, we have solved the crystal structure of the SMChd to 3.1 A resolution. In the monoclinic crystal form, six SMChd molecules form two turns of a helix. The fold of SMChd is closely related to the ATP-binding cassette (ABC) ATPase family of proteins and Rad50, a member of the SMC family involved in DNA double-strand break repair. In SMChd, the ABC ATPase fold is formed by the N and C-terminal domains with the 900 residue coiled-coil and hinge segment inserted in the middle of the fold. The crystal structure of an SMChd confirms that the coiled-coil segments in SMC proteins are anti-parallel and shows how the N and C-terminal domains come together to form an ABC ATPase. Comparison to the structure of the MukB N-terminal domain demonstrates the close relationship between MukB and SMC proteins, and indicates a helix to strand conversion when N and C-terminal parts come together.
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PMID:Crystal structure of the SMC head domain: an ABC ATPase with 900 residues antiparallel coiled-coil inserted. 1117 91

Sister chromatids are held together by the multisubunit cohesin complex, which contains two SMC (Smc1 and Smc3) and two non-SMC (Scc1 and Scc3) proteins. The crystal structure of a bacterial SMC "hinge" region along with EM studies and biochemical experiments on yeast Smc1 and Smc3 proteins show that SMC protamers fold up individually into rod-shaped molecules. A 45 nm long intramolecular coiled coil separates the hinge region from the ATPase-containing "head" domain. Smc1 and Smc3 bind to each other via heterotypic interactions between their hinges to form a V-shaped heterodimer. The two heads of the V-shaped dimer are connected by different ends of the cleavable Scc1 subunit. Cohesin therefore forms a large proteinaceous loop within which sister chromatids might be entrapped after DNA replication.
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PMID:Molecular architecture of SMC proteins and the yeast cohesin complex. 1198 69

A multisubunit complex called cohesin forms a huge ring structure that mediates sister chromatid cohesion, possibly by entrapping sister DNAs following replication. Cohesin's kleisin subunit Scc1 completes the ring, connecting the ABC-like ATPase heads of a V-shaped Smc1/3 heterodimer. Proteolytic cleavage of Scc1 by separase triggers sister chromatid disjunction, presumably by breaking the Scc1 bridge. One half of the SMC-kleisin bridge is revealed here by a crystal structure of Smc1's ATPase complexed with Scc1's C-terminal domain. The latter forms a winged helix that binds a pair of beta strands in Smc1's ATPase head. Mutation of conserved residues within the contact interface destroys Scc1's interaction with Smc1/3 heterodimers and eliminates cohesin function. Interaction of Scc1's N terminus with Smc3 depends on prior C terminus connection with Smc1. There is little or no turnover of Smc1-Scc1 interactions within cohesin complexes in vivo because expression of noncleavable Scc1 after DNA replication does not hinder anaphase.
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PMID:Structure and stability of cohesin's Smc1-kleisin interaction. 1538 84

We isolated several related but distinct cDNA clones encoding novel structure proteins (NSP) when screening a cDNA library. Analysis revealed that these cDNAs and several similar ESTs in the public databases are derived from a single gene of 17 exons that span a minimum of 227-kb region. This gene is located at chromosome 17p11.2, a region frequently amplified in human gliomas and osteosarcomas, and involved in Birt-Hogg-Dube syndrome, a tumor-prone syndrome. The major coding sequences shared by all isolated transcripts are predicted to encode SMC (structural maintenance of chromosome)/SbcC ATPase motifs and coiled-coil domains commonly seen in motor or structure proteins. Two 5'-end and two 3'-end variants (type 5alpha/beta and 3alpha/beta, respectively) were identified, making a total of four possible transcripts. Both 5alpha and 5beta variants were detected in human testis mRNA, but only type 5alpha was detectable in RNA samples extracted from HeLa cells. The unique carboxyl-terminus of 3beta contains a Ca(2+)-dependent actin-binding domain. Immunohistochemistry studies revealed that NSPs were mostly localized to nuclei. Northern blot analysis demonstrated two major bands and the expression levels are tremendously high in testis while barely detectable in other normal tissues examined. Interestingly, NSP5alpha3alpha is highly expressed in some tumor cell lines. These results suggest that NSPs represent a new family of structure proteins with a possible role in nuclear dynamics during cell division, and that NSP5alpha3alpha may serve as a tumor marker.
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PMID:A gene highly expressed in tumor cells encodes novel structure proteins. 1560 74

The Escherichia coli MukB, MukE, and MukF proteins form a bacterial condensin (MukBEF) that contributes to chromosome management by compacting DNA. MukB is an ATPase and DNA-binding protein of the SMC superfamily; however, the structure and function of non-SMC components, such as MukF, have been less forthcoming. Here, we report the crystal structure of the N-terminal 287 amino acids of MukF at 2.9 A resolution. This region folds into a winged-helix domain and an extended coiled-coil domain that self-associate to form a stable, doubly domain-swapped dimer. Protein dissection and affinity purification data demonstrate that the region of MukF C-terminal to this fragment binds to MukE and MukB. Our findings, together with sequence analyses, indicate that MukF is a kleisin subunit for E. coli condensin and suggest a means by which it may organize the MukBEF assembly.
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PMID:The MukF subunit of Escherichia coli condensin: architecture and functional relationship to kleisins. 1590 72


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