Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two electrophoretic variants of the 6-phosphogluconate dehydrogenase (6 PGD) enzyme have been found in the WHO/IN/Musca domestica/l housefly laboratory strain. The patterns shown by Cellogel zone electrophoresis can be fully explained by the hypothesis of two codominant autosomal alleles. On this hypothesis, a specific Pgd locus has been postulated and the symbols PgdA and PgdB have been assigned to the two alleles causing the PGD-A and PGD-B phenotypes. The bands corresponding to the homozygous phenotypes PGD-A and PGD-B have different electrophoretic mobility and staining intensity; they can be described, respectively, as "fast-weak" and "slow-thick." The heterozygous phenotype PGD-AB gives a three-banded pattern, indicative of a dimeric structure for this enzyme; this pattern is asymmetrical. Heterozygous flies have been found both among wild-type strains of recent colonization and among old established laboratory colonies. Most strains are PgdB monomorphic; up to now only three strains have been PgdA monomorphic, all of them being multimarker strains. The Pgd locus has been traced to the housefly linkage group III.
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PMID:6-phosphogluconate dehydrogenase in the housefly, Musca domestica L.:evidence for inheritable 6PGD polymorphism. 54 22

The orientation of the principal axes of the primary electron donor triplet state measured in single crystals of photosynthetic reaction centers is compared to the x-ray structures of the bacteria Rhodobacter (Rb.) sphaeroides R-26 and Rhodopseudomonas (Rps.) viridis. The primary donor of Rps. viridis is significantly different from that of Rb. sphaeroides. The measured directions of the axes indicate that triplet excitation is almost completely localized on the L-subunit half of the dimer in Rps. viridis but is more symmetrically distributed (approximately 63% on the L half of the special pair and approximately 37% on the M half) on the dimeric donor in Rb. sphaeroides R-26. The large reduction of the zero field splitting parameters relative to monomeric bacteriochlorophyll triplet in vitro suggests significant participation of asymmetrical charge transfer electronic configurations in the special pair triplet state of both organisms (approximately 23% in Rps. viridis and approximately 13% in Rb. sphaeroides).
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PMID:Correlation of paramagnetic states and molecular structure in bacterial photosynthetic reaction centers: the symmetry of the primary electron donor in Rhodopseudomonas viridis and Rhodobacter sphaeroides R-26. 254 69

The untransformed rat glucocorticoid receptor is assumed to be a hetero-oligomeric complex, containing a non-steroid binding component, the 90K heat-shock protein (HSP 90). Direct measurement of its molecular weight by chemical cross-linking provides new evidence for a trimeric structure with a Mr of ca. 270,000. Resorting to an anti HSP 90 probe (AC 88), we show that the native dimeric HSP 90 possess two accessible epitopes for this monoclonal antibody, while when bound to the steroid-binding subunit, only one epitope remains accessible. These data clearly suggest that the untransformed rat glucocorticoid receptor is an asymmetrical hetero-oligomeric complex.
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PMID:Study of the heteromeric structure of the untransformed glucocorticoid receptor using chemical cross-linking and monoclonal antibodies against the 90K heat-shock protein. 293 May 36

Carbon monoxide binding to Chromatium vinosum ferrocytochrome c' has been studied by high-precision equilibrium methods. In contrast to the CO binding properties of Rhodospirillum molischianum cytochrome c' [Doyle, M. L., Weber, P. C., & Gill, S. J. (1985) Biochemistry 24, 1987-1991], CO binding to C. vinosum cytochrome c' is found to be unusual in the following ways. The binding curve is found to be cooperative with typical Hill coefficients equal to 1.25. The shape of the binding curve is asymmetrical. The heat of CO ligation is measured by two independent methods, both of which yield large endothermic values of approximately 10 kcal [mol of CO(aq)]-1. The overall affinity for CO increases as the concentration of cytochrome c' decreases. These observations suggest the CO binding properties of C. vinosum cytochrome c' are complicated by CO-linked association-dissociation processes. Further investigation by gel filtration chromatography shows that at micromolar concentrations the dimeric state is tightly associated in both the reduced and oxidized forms of the cytochrome but addition of saturating concentrations of CO causes the reduced ligated dimer to dissociate largely into monomers. A model is presented that quantitatively fits the data, involving a ligand-linked dimer-monomer dissociation reaction. In this model, CO binds to the dimer form noncooperatively with an intrinsic affinity constant equal to 5600 +/- 1200 M-1 at 25 degrees C. The unligated dimer form is tightly associated, but addition of CO causes dissociation of the dimer into the monomer with a monomer-dimer association constant equal to 450 +/- 200 M-1.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ligand-controlled dissociation of Chromatium vinosum cytochrome c'. 301 6

Ditercalinium and its analogues are dimeric molecules made up of two identical 7H-pyrido[4,3-c]carbazole rings linked by symmetrical linking chains. These dimers elicit antitumor properties through a new mechanism of action. Recently, a relationship was found between their antitumor properties and their cytotoxic effect on the polA Escherichia coli mutant strain, suggesting that 7H-pyrido[4,3-c]carbazole dimers might induce a DNA deformation that could be recognized by the E. coli SOS repair system. Thus, the role of symmetry in ditercalinium analogues for their DNA binding, antitumor properties, and bacterial toxicity is investigated in the present study, by introducing asymmetric parameters in their structures. Dimers were either synthesized with an asymmetrical rigid linking chain or made up of two chemically different chromophores, i.e., acridine and 7H-pyrido[4,3-c]carbazole. The asymmetrical dimers remain able to bisintercalate into DNA with high affinities, but a dramatic loss in their antitumor potency is observed. On the other hand, these asymmetrical dimers are cytotoxic for polA E. coli mutants, like their symmetrical analogues. These results show that the symmetry plays a crucial role for the antitumor potency in the 7H-pyrido[4,3-c]carbazole dimers series.
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PMID:Asymmetrical bisintercalators as potential antitumor agents. 328 64

The structure and molecular interactions of the primary donor (P680) in the reaction center (D1-D2-cytochrome b-559 complex) of photosystem II (PS II) have been investigated by detecting light-induced FT-IR difference spectra upon the formation of its triplet state (3P680). The 3P680/P680 spectrum obtained was analyzed by comparing it with difference spectra between the ground and lowest triplet states of purified chlorophyll a (Chl) in organic solvents. The negative peaks at 1669 and 1707 cm-1 accompanied by the positive peaks at 1627 and 1659 cm-1 in the 3P680/P680 spectrum were assigned to the keto C = O stretching mode, and the appearance of these two pairs of bands indicated that P680 has a dimeric structure analogous to that of the bacterial primary donor. From the band positions of the keto and carbomethoxy C = O stretches, the hydrogen-bonding properties of these two Chl molecules were found to be asymmetrical; in one Chl molecule both the keto and carbomethoxy C = O groups form hydrogen bonds, while in the other Chl molecule the keto C = O is not hydrogen-bonded whereas the carbomethoxy C = O probably is hydrogen-bonded. The temperature dependence of the intensity ratios of the keto C = O bands revealed that the triplet state is equilibrated between the two Chl molecules with an energy gap of 8.4 +/- 0.7 meV. Most of the triplet population was found to be localized on one Chl molecule (86% at 80 K), in which both of the two C = O groups are hydrogen-bonded, that is probably attached to the D1 subunit. Considering the structure of the bacterial reaction center determined by X-ray crystallography and the sequence homology between the D1 and D2 subunits of PS II and the L and M subunits of bacteria, a model of the P680 structure and its interactions with apoproteins has been proposed.
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PMID:FT-IR studies on the triplet state of P680 in the photosystem II reaction center: triplet equilibrium within a chlorophyll dimer. 834 8

Mammalian alkaline phosphatases (APs) are zinc-containing metalloenzymes encoded by a multigene family and functional as dimeric molecules. Using human placental AP (PLAP) as a paradigm, we have investigated whether the monomers in a given PLAP dimer are subject to cooperativity during catalysis following an allosteric model or act via a half-of-sites model, in which at any time only one single monomer is operative. Wild type and mutant PLAP homodimers and heterodimers were produced by stably transfecting Chinese hamster ovary cells with mutagenized PLAP cDNAs followed by enzyme extraction, purification, and characterization. [Gly429]PLAP manifested negative cooperativity when partially metalated as a consequence of the reduced affinity of the incompletely metalated AP monomers for the substrate. Upon full metalation with Zn2+, however, the negative cooperativity disappeared. To distinguish between an allosteric and a half-of-sites model, a [Gly429]PLAP-[Ser84]PLAP heterodimer was produced by combining monomers displaying high and low sensitivity to the uncompetitive inhibitor L-Leu as well as a [Gly429]PLAP-[Ala92]PLAP heterodimer combining a catalytically active and inactive monomer, respectively. The L-Leu inhibition profile of the [Gly429]PLAP-[Ser84]PLAP heterodimer was intermediate to that for each homodimer as predicted by the allosteric model. Likewise, the [Gly429]PLAP-[Ala92]PLAP heterodimer was catalytically active, confirming that AP monomers act independently of each other. Although heterodimers are structurally asymmetrical, they migrate in starch gels with a smaller than expected weighted electrophoretic mobility, are more stable to heat denaturation than expected, and are more sensitive to L-Leu inhibition than predicted by a strict noncooperative model. We conclude that fully metalated mammalian APs are noncooperative allosteric enzymes but that the stability and catalytic properties of each monomer are controlled by the conformation of the second AP subunit.
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PMID:Mammalian alkaline phosphatases are allosteric enzymes. 927 39

Very pure, detergent-solubilized Na,K-ATPase from dog or lamb kidneys has been successfully reconstituted at high protein-to-lipid weight ratios. Studies have been conducted to establish the orientation of the Na,K-ATPase molecules in the reconstituted membranes and to assess the functional activity and the conformational state of the reconstituted enzyme. Results indicate that reincorporation of the Na,K-ATPase molecules in the lipid bilayer is unidirectional and that the reconstituted enzyme retains its functional and structural integrity. Two-dimensional crystals have been induced in these preparations by vanadate ions. The arrays, with a dimeric structure in the unit cell, have a morphology similar to that of the crystals that had previously formed in the native membranes. Filtered images show that in projection, the molecule had an asymmetrical mass distribution, which at the resolution of 2.5 nm is identical to that of the earlier crystals. These sheets, although small, represent the first crystals of Na, K-ATPase to be formed by reconstitution. We expect that optimization of the reconstitution and crystallization parameters will lead to larger and better-ordered sheets, suitable for electron crystallography.
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PMID:Reconstitution of detergent-solubilized Na,K-ATPase and formation of two-dimensional crystals. 1019 18

Interaction of T4 DNA-(N6-adenine)-methyltransferase [EC 2.1.1] was studied with a variety of synthetic oligonucleotide substrates containing the native recognition site GATC or its modified variants. The data obtained in the decisecond and second intervals of the reaction course allowed for the first time the substrate methylation rates to be compared with the parameters of the steady-state reaction. It was established that the substrate reaction proceeds in two stages. Because it is shown that in steady-state conditions T4 MTase forms a dimeric structure, the following sequence of events is assumed. Upon collision of a T4 MTase monomer with an oligonucleotide duplex, an asymmetrical complex forms in which the enzyme randomly oriented relative to one of the strands of the specific recognition site catalyzes a fast transfer of the methyl group from S-adenosylmethionine to the adenosine residue (k1 = 0.21 s-1). Simultaneously, a second T4 MTase subunit is added to the complex, providing for the continuation of the reaction. In the course of a second stage, which is by an order of magnitude slower (k2 = 0.023 s-1 for duplex with the native site), the dimeric T4 MTase switches over to the second strand and the methylation of the second residue, target. The rate of the methyl group transfer from donor, S-adenosylmethionine, to DNA is much higher than the overall rate of the T4 MTase-catalyzed steady-state reaction, although this difference is considerably less than that shown for EcoRI Mtase. Substitutions of bases and deletions in the recognition site affect the substrate parameters in different fashions. When the GAT sequence is disrupted, the proportion of the initial productive enzyme-substrate complexes is usually sharply reduced. The flipping of the adenosine residue, a target for the modification in the recognition site, revealed by fluorescence titration, upon interaction with the enzyme supports the existing notions about the involvement of such a DNA deformation in reactions catalyzed by various DNA-MTases.
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PMID:[Single turnover kinetics of phage T4 DNA-(N6-adenine)methyltransferase]. 1123 84

Estrogen-induced signaling mediated by estrogen receptors (ERs) is also affected by aberrant ERs that act as constitutively active or dominant negative modulators. Variant ERs can contribute to carcinogenesis and to the loss of estrogen responsiveness, rendering antiestrogen therapy ineffective. Determining target gene response during co-synthesis of different ER species is difficult, because dimers formed in the presence of more than one ER species are a heterogenous population of homo- or heterodimers. We engineered a homofusion ERalpha as a prototype single-chain receptor by genetically conjugating two ER monomers into a covalently fused single-chain protein to obtain a homogeneous population. This permits analysis of symmetrical or asymmetrical mutations that simulate variant homo- and heterodimers. Although a monomer, the homofusion receptor exhibited similar biochemical and functional properties to the dimeric ERalpha. We used activation function-2 (AF2) defective mutants as a model in either one or both receptor domains for a dominant-negative phenotype by suppressing the reporter activity induced by the WT receptor. When co-expressed with ERalpha, the fusion variant deficient in both AF2 functions suppressed the reporter activity effectively induced by ERalpha. These results show the utility of fusion receptors as models for generation of receptor-based agonists and antagonists.
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PMID:Fusion estrogen receptor proteins: toward the development of receptor-based agonists and antagonists. 1151 59


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