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1.
M. Rybák E. Kasafirek B. Rybáková E. Simonianová 《Cellular and molecular life sciences : CMLS》1979,35(8):996-997
Summary The use of dipeptide-p-nitranilides for the study of 2 placental aminopeptidases separated on Sephadex G200 helped in establishing some regular features of their specifities. The high-molecular (320,000 daltons) one prefers Phe in position P'1 to Leu, whereas the lower-molecular aminopeptidase (145,000 daltons) prefers Leu. The high-molecular aminopeptidase splits very slowly the N-terminal Leu when Gly is in adjacent position. Leu-Gly-p-NA is therefore an inhibitor of this AP. 相似文献
2.
Zusammenfassung Antibiotikum U-22324 ist ein zyklisches Peptid, das aus Kulturflüssigkeit vonTrichoderma viride isoliert wurde. Das Peptid hat die Aminosäurenzusammensetzung (GluN)2(Glu)1(Pro)2(Gly)1(Ala)2(Dimethyl ala)8(Val)2(Leu)1. 相似文献
3.
Sergio Porté Agrin Moeini Irene Reche Naeem Shafqat Udo Oppermann Jaume Farrés Xavier Parés 《Cellular and molecular life sciences : CMLS》2011,68(6):1065-1077
Human ζ-crystallin is a Zn2+-lacking medium-chain dehydrogenase/reductase (MDR) included in the quinone oxidoreductase (QOR) family because of its activity
with quinones. In the present work a novel enzymatic activity was characterized: the double bond α,β-hydrogenation of medium-chain
2-alkenals and 3-alkenones. The enzyme is especially active with lipid peroxidation products such as 4-hydroxyhexenal, and
a role in their detoxification is discussed. This specificity is novel in the QOR family, and it is similar to that described
in the distantly related alkenal/one reductase family. Moreover, we report the X-ray structure of ζ-crystallin, which represents
the first structure solved for a tetrameric Zn2+-lacking MDR, and which allowed the identification of the active-site lining residues. Docking simulations suggest a role
for Tyr53 and Tyr59 in catalysis. The kinetics of Tyr53Phe and Tyr59Phe mutants support the implication of Tyr53 in binding/catalysis
of alkenal/one substrates, while Tyr59 is involved in the recognition of 4-OH-alkenals. 相似文献
4.
Unique evolution of Bivalvia arginine kinases 总被引:1,自引:0,他引:1
Takeuchi M Mizuta C Uda K Fujimoto N Okamoto M Suzuki T 《Cellular and molecular life sciences : CMLS》2004,61(1):110-117
The clams Pseudocardium, Solen, Corbicula and Ensis possess a unique form of arginine kinase (AK) with a molecular mass of 80 kDa and an unusual two-domain structure, a result of gene duplication and subsequent fusion. These AKs also lack two functionally important amino acid residues, Asp62 and Arg193, which are strictly conserved in other 40-kDa AKs and are assumed to be key residues for stabilizing the substrate-bound structure. However, these AKs show higher enzyme activity. The cDNA-derived amino acid sequences of 40-kDa AKs from the blood clam Scapharca broughtonii and the oyster Crassostrea gigas were determined. While Asp62 and Arg193 are conserved in Scapharca AK, these two key residues are replaced by Asn and Lys, respectively, in Crassostrea AK. The native enzyme from Crassostrea and both of the recombinant enzymes show an enzyme activity similar to that of two-domain clam AKs and at least twofold higher than that of other molluskan AKs. Although the replacement of Asp62 or Arg193 by Gly in normal AK causes a considerable decrease in Vmax (6–15% of wild-type enzyme) and a two- to threefold increase in Km for arginine, the same replacement in Scapharca AK had no pronounced effect on enzyme activity. Together with the observation that bivalve AKs are phylogenetically distinct from other molluskan AKs, these results suggest that bivalve AKs have undergone a unique molecular evolution; the characteristic stabilizing function of residues 62 and 193 has been lost and, consequently, the enzyme shows higher activity than normal.Received 14 October 2003; accepted 1 November 2003 相似文献
5.
The type I copper center in multicopper oxidases is constructed from 1Cys2His and weakly coordinating 1Met or the non-coordinating 1Phe/1Leu, and it exhibits spectral properties and an alkaline transition similar to those of the blue copper center in blue copper proteins. Since the type I copper center in multicopper oxidases is deeply buried inside the protein molecule, electron transfers to and from type I copper are performed through specific pathways: the hydrogen bond between an amino acid located at the substrate binding site and a His residue coordinating type I copper, and the His-Cys-His sequence connecting the type I copper center and the trinuclear copper center comprised of a type II copper and a pair of type III coppers. The intramolecular electron transfer rates can be tuned by mutating the fourth ligand of type I copper. Further, mutation at the Cys ligand gives a vacant type I copper center and traps the reaction intermediate during the four-electron reduction of dioxygen. 相似文献
6.
The use of dipeptide-p-nitranilides for the study of 2 placental aminopeptidases separated on Sephadex G200 helped in establishing some regular features of their specifities. The high-molecular (320,000 daltons) one prefers Phe in position P'1 to Leu, whereas the lower-molecular aminopeptidase (145,000 daltons) prefers Leu. The high-molecular aminopeptidase splits very slowly the N-terminal Leu when Gly is in adjacent position. Leu-Gly-p-NA is therefore an inhibitor of this AP. 相似文献
7.
Sangeeta Chauhan Xinde Zheng Yue Ying Tan Boon-Hui Tay Shuhui Lim Byrappa Venkatesh Philipp Kaldis 《Cellular and molecular life sciences : CMLS》2012,69(22):3835-3850
Successful completion of the cell cycle relies on the precise activation and inactivation of cyclin-dependent kinases (Cdks) whose activity is mainly regulated by binding to cyclins. Recently, a new family of Cdk regulators termed Speedy/RINGO has been discovered, which can bind and activate Cdks but shares no apparent amino acid sequence homology with cyclins. All Speedy proteins share a conserved domain of approximately 140 amino acids called “Speedy Box”, which is essential for Cdk binding. Speedy/RINGO proteins display an important role in oocyte maturation in Xenopus. Interestingly, a common feature of all Speedy genes is their predominant expression in testis suggesting that meiotic functions may be the most important physiological feature of Speedy genes. Speedy homologs have been reported in mammals and can be traced back to the most primitive clade of chordates (Ciona intestinalis). Here, we investigated the evolution of the Speedy genes and have identified a number of new Speedy/RINGO proteins. Through extensive analysis of numerous species, we discovered diverse evolutionary histories: the number of Speedy genes varies considerably among species, with evidence of substantial gains and losses. Despite the interspecies variation, Speedy is conserved among most species examined. Our results provide a complete picture of the Speedy gene family and its evolution. 相似文献
8.
Toniolo C Crisma M Formaggio F Peggion C Epand RF Epand RM 《Cellular and molecular life sciences : CMLS》2001,58(9):1179-1188
Lipopeptaibols are members of a novel group of naturally occurring, short peptides with antimicrobial activity, characterized
by a lipophilic acyl chain at the N-terminus, a high content of the turn/helix forming α-aminoisobutyric acid and a 1,2-amino alcohol at the C-terminus. The amino acid sequences range from 6 to 10 residues and
the fatty acyl moieties from 8 to 15 carbon atoms. The peptide portion of lipopeptaibols can be shorter than those of the
nonlipidated peptaibols that range from 10 to 19 amino acid residues. The longest peptides fold into a mixed 310/α helix, whereas the shortest peptides tend to adopt a β-turn/sheet structure. Using solution methodologies, a series of analogues of trichogin GA IV was synthesized which allowed
determination of the minimal lipid chain and peptide main-chain lengths for the onset of membrane activity and exploitation
of a number of spectroscopic techniques aimed at determining its preferred conformation under a variety of conditions and
investigating in detail its mode of interaction with, and its effect on, the phospholipid membranes.
Received 26 January 2001; received after revision 7 March 2001; accepted 15 March 2001 相似文献
9.
Yoshida Y Obita T Kokusho Y Ohmura T Katayama T Ueda T Imoto T 《Cellular and molecular life sciences : CMLS》2003,60(9):1998-2008
DnaA protein binds specifically to a 9-base- pair motif called the DnaA box. Domain IV comprises 94 amino acid residues and is required for DNA binding. Using nuclear magnetic resonance analysis, we investigated the interaction between DnaA domain IV and both a DnaA box and a non-specific oligonucleotide that has a reduced affinity for DnaA. The 1H-15N HSQC spectrum of DnaA domain IV showed prominent chemical shift perturbations on six residues (Arg399, Ala404, Leu422, Asp433, Thr435 and Thr436) in the presence of the DnaA box. Through homology modeling, we located all of these residues on one side surface of the DnaA domain IV molecule. Moreover, we compared the chemical shift perturbation of the 1H-15N HSQC spectrum in the presence of the DnaA box with that in the presence of a non-specific oligonucleotide, and the results suggested that Leu422 imparts specificity in binding with the DnaA box.Received 6 May 2003; received after revision 18 June 2002; accepted 4 July 2003 相似文献
10.
Shilpa Bali David J. Palmer Susanne Schroeder Stuart J. Ferguson Martin J. Warren 《Cellular and molecular life sciences : CMLS》2014,71(15):2837-2863
Hemes (a, b, c, and o) and heme d 1 belong to the group of modified tetrapyrroles, which also includes chlorophylls, cobalamins, coenzyme F430, and siroheme. These compounds are found throughout all domains of life and are involved in a variety of essential biological processes ranging from photosynthesis to methanogenesis. The biosynthesis of heme b has been well studied in many organisms, but in sulfate-reducing bacteria and archaea, the pathway has remained a mystery, as many of the enzymes involved in these characterized steps are absent. The heme pathway in most organisms proceeds from the cyclic precursor of all modified tetrapyrroles uroporphyrinogen III, to coproporphyrinogen III, which is followed by oxidation of the ring and finally iron insertion. Sulfate-reducing bacteria and some archaea lack the genetic information necessary to convert uroporphyrinogen III to heme along the “classical” route and instead use an “alternative” pathway. Biosynthesis of the isobacteriochlorin heme d 1, a cofactor of the dissimilatory nitrite reductase cytochrome cd 1, has also been a subject of much research, although the biosynthetic pathway and its intermediates have evaded discovery for quite some time. This review focuses on the recent advances in the understanding of these two pathways and their surprisingly close relationship via the unlikely intermediate siroheme, which is also a cofactor of sulfite and nitrite reductases in many organisms. The evolutionary questions raised by this discovery will also be discussed along with the potential regulation required by organisms with overlapping tetrapyrrole biosynthesis pathways. 相似文献
11.
L. Dhers L. Ducassou J.-L. Boucher D. Mansuy 《Cellular and molecular life sciences : CMLS》2017,74(10):1859-1869
Cytochrome P450 2U1 (CYP2U1) exhibits several distinctive characteristics among the 57 human CYPs, such as its presence in almost all living organisms with a highly conserved sequence, its particular gene organization with only five exons, its major location in thymus and brain, and its protein sequence involving an unusually long N-terminal region containing 8 proline residues and an insert of about 20 amino acids containing 5 arginine residues after the transmembrane helix. Few substrates, including fatty acids, N-arachidonoylserotonin (AS), and some drugs, have been reported so far. However, its biological roles remain largely unknown, even though CYP2U1 mutations have been involved in some pathological situations, such as complicated forms of hereditary spastic paraplegia. These data together with its ability to hydroxylate some fatty acids and AS suggest its possible role in lipid metabolism. 相似文献
12.
Caitlin Collin Frank Hauser Ernesto Gonzalez de Valdivia Shizhong Li Julia Reisenberger Eva M. M. Carlsen Zaid Khan Niels Ø. Hansen Florian Puhm Leif Søndergaard Justyna Niemiec Magdalena Heninger Guilin R. Ren Cornelis J. P. Grimmelikhuijzen 《Cellular and molecular life sciences : CMLS》2013,70(17):3231-3242
Muscarinic acetylcholine receptors (mAChRs) play a central role in the mammalian nervous system. These receptors are G protein-coupled receptors (GPCRs), which are activated by the agonists acetylcholine and muscarine, and blocked by a variety of antagonists. Mammals have five mAChRs (m1–m5). In this study, we cloned two structurally related GPCRs from the fruit fly Drosophila melanogaster, which, after expression in Chinese hamster ovary cells, proved to be muscarinic acetylcholine receptors. One mAChR (the A-type; encoded by gene CG4356) is activated by acetylcholine (EC50, 5 × 10?8 M) and muscarine (EC50, 6 × 10?8 M) and blocked by the classical mAChR antagonists atropine, scopolamine, and 3-quinuclidinyl-benzilate (QNB), while the other (the B-type; encoded by gene CG7918) is also activated by acetylcholine, but has a 1,000-fold lower sensitivity to muscarine, and is not blocked by the antagonists. A- and B-type mAChRs were also cloned and functionally characterized from the red flour beetle Tribolium castaneum. Recently, Haga et al. (Nature 2012, 482: 547–551) published the crystal structure of the human m2 mAChR, revealing 14 amino acid residues forming the binding pocket for QNB. These residues are identical between the human m2 and the D. melanogaster and T. castaneum A-type mAChRs, while many of them are different between the human m2 and the B-type receptors. Using bioinformatics, one orthologue of the A-type and one of the B-type mAChRs could also be found in all other arthropods with a sequenced genome. Protostomes, such as arthropods, and deuterostomes, such as mammals and other vertebrates, belong to two evolutionarily distinct lineages of animal evolution that split about 700 million years ago. We found that animals that originated before this split, such as cnidarians (Hydra), had two A-type mAChRs. From these data we propose a model for the evolution of mAChRs. 相似文献
13.
Plasticins belong to the dermaseptin superfamily of gene-encoded, membrane-active host defense peptides produced by the skin
of hylid frogs. The plasticins, which are rich in Gly and Leu residues arranged in regular 5-mer motifs GXXXG (where X is
any amino acid residue), have very similar amino acid sequences, hydrophobicities, and amphipathicities but differ markedly
in their net charge, conformational plasticity, and activity spectra. The intrinsic flexibility and structural malleability
of plasticins modulate their ability to bind to and disrupt the membranes of prokaryotic and eukaryotic cells, and/or to reach
intracellular targets, therefore triggering functional versatility. This family of closely related but functionally divergent
peptides constitutes a good model to address the relationships between structural polymorphism, membrane-interacting properties,
and the biological activity of antimicrobial, cell-penetrating, and viral fusion peptides. Plasticins could thus serve as
templates to design potent multifunctional drugs that could act simultaneously against bacterial pathogens and viruses.
Received 26 September 2007; received after revision 22 October 2007; accepted 29 October 2007 相似文献
14.
Hellgren M Kaiser C de Haij S Norberg A Höög JO 《Cellular and molecular life sciences : CMLS》2007,64(23):3129-3138
Subunit interaction in sorbitol dehydrogenase (SDH) has been studied with in vitro and in silico methods identifying a vital hydrogen-bonding network, which is strictly conserved among mammalian SDH proteins. Mutation
of one of the residues in the hydrogen-bonding network, Tyr110Phe, abolished the enzymatic activity and destabilized the protein
into tetramers, dimers and monomers as judged from gel filtration experiments at different temperatures compared to only tetramers
for the wild-type protein below 307 K. The determined equilibrium constants revealed a large difference in Gibbs energy (8
kJ/mol) for the tetramer stability between wild-type SDH and the mutated form Tyr110Phe SDH. The results focus on a network
of coupled hydrogen bonds in wild-type SDH that uphold the protein interface, which is specific and favorable to electrostatic,
van der Waals and hydrogen-bond interactions between subunits, interactions that are crucial for the catalytic power of SDH.
Received 13 July 2007; received after revision 30 September 2007; accepted 1 October 2007 相似文献
15.
Christian Piehl Jörg Piontek Jimmi Cording Hartwig Wolburg Ingolf E. Blasig 《Cellular and molecular life sciences : CMLS》2010,67(12):2131-2140
Tight junctions control paracellular permeability. Here, we analyzed the impact of residues in the second extracellular loop
(ECL2) of mouse claudin-5 on paracellular permeability. Stable expression of claudin-5wild type in MDCK-II cells—but not that of mutants R145A, Y148A, Y158A or E159Q—increased transepithelial electrical resistance and
decreased fluorescein permeation. Expression of claudin-5Y148A, Y158A or E159Q enhanced permeability of FITC-dextran10 kDa, which was unchanged in cells expressing claudin-5wild type or claudin-5R145A. In contrast, targeting to tight junctions, strand morphology and tight junction assembly were unchanged. It is concluded
that R145 is unessential for trans-interaction of claudin-5, but necessary for tightening against small solutes and ions. The highly conserved residues Y148,
Y158 and E159 in ECL2 of claudin-5 contribute to homo- and/or heterophilic trans-interaction between classic claudins and thereby tighten the paracellular space against ions, small and large molecules.
These results provide novel insights into the molecular function of tight junctions. 相似文献
16.
Rob Houtmeyers Jacob Souopgui Sabine Tejpar Ruth Arkell 《Cellular and molecular life sciences : CMLS》2013,70(20):3791-3811
The zinc finger of the cerebellum gene (ZIC) discovered in Drosophila melanogaster (odd-paired) has five homologs in Xenopus, chicken, mice, and humans, and seven in zebrafish. This pattern of gene copy expansion is accompanied by a divergence in gene and protein structure, suggesting that Zic family members share some, but not all, functions. ZIC genes are implicated in neuroectodermal development and neural crest cell induction. All share conserved regions encoding zinc finger domains, however their heterogeneity and specification remain unexplained. In this review, the evolution, structure, and expression patterns of the ZIC homologs are described; specific functions attributable to individual family members are supported. A review of data from functional studies in Xenopus and murine models suggest that ZIC genes encode multifunctional proteins operating in a context-specific manner to drive critical events during embryogenesis. The identification of ZIC mutations in congenital syndromes highlights the relevance of these genes in human development. 相似文献
17.
Pepsinogens, progastricsins, and prochymosins: structure, function, evolution, and development 总被引:12,自引:0,他引:12
Kageyama T 《Cellular and molecular life sciences : CMLS》2002,59(2):288-306
Five types of zymogens of pepsins, gastric digestive proteinases, are known: pepsinogens A, B, and F, progastricsin, and
prochymosin. The amino acid and/or nucleotide sequences of more than 50 pepsinogens other than pepsinogen B have been determined
to date. Phylogenetic analyses based on these sequences indicate that progastricsin diverged first followed by prochymosin,
and that pepsinogens A and F are most closely related. Tertiary structures, clarified by X-ray crystallography, are commonly
bilobal with a large active-site cleft between the lobes. Two aspartates in the center of the cleft, Asp32 and Asp215, function
as catalytic residues, and thus pepsinogens are classified as aspartic proteinases. Conversion of pepsinogens to pepsins proceeds
autocatalytically at acidic pH by two different pathways, a one-step pathway to release the intact activation segment directly,
and a stepwise pathway through a pseudopepsin(s). The active-site cleft is large enough to accommodate at least seven residues
of a substrate, thus forming S4 through S3′ subsites. Hydrophobic and aromatic amino acids are preferred at the P1 and P1′ positions. Interactions at additional subsites are important in some cases, for example with cleavage of κ-casein by chymosin. Two potent naturally occurring inhibitors are known: pepstatin, a pentapeptide from Streptomyces, and a unique proteinous inhibitor from Ascaris. Pepsinogen genes comprise nine exons and may be multiple, especially for pepsinogen A. The latter and progastricsin predominate
in adult animals, while pepsinogen F and prochymosin are the main forms in the fetus/infant. The switching of gene expression
from fetal/infant to adult-type pepsinogens during postnatal development is noteworthy, being regulated by several factors,
including steroid hormones.
Received 25 May 2001; received after revision 27 August 2001; accepted 30 August 2001 相似文献
18.
D. Podhradský Ľ. Drobnica P. Kristian 《Cellular and molecular life sciences : CMLS》1979,35(2):154-155
Summary Isothiocyanates react with deprotonated SH groups of investigated compounds to give the esters of N-monosubstituted dithiocarbamic acid. In the presence of the SH and NH2 groups (Cys, GSH), isothiocyanates react primarily with the SH groups. The reactions are dependent on the pKaSH values. 相似文献
19.
M. Hallman P. Mäenpää I. Hassinen 《Cellular and molecular life sciences : CMLS》1972,28(12):1408-1410
Zusammenfassung Der Gehalt an Cytochromen (c+c
1,aa
3 undb) in Herz, Leber, Gehirn und Niere der Ratte wurde bestimmt. Ihre Vermehrung nach der Geburt erwies sich in den Geweben als relativ individuell. Die Vermehrung des ausserhalb der Mitochondrien synthetisierten Cytochromenc ging den übrigen, von der intramitochondrialen Proteinsynthese unabhängigen Cytochromen voraus. 相似文献
20.
D. Bernard J. -C. Maurizis C. Nicolas J. Michelot G. Bétail G. Meyniel 《Cellular and molecular life sciences : CMLS》1985,41(3):385-387
Summary Antibodies reacting with 3,5,3,5 tetraiodo-l-tyrosyl-l-tyrosine (I2Tyr-I2Tyr) were elicited in rabbits by immunization with an oxidized yeast conjugate coupled with I2Tyr-I2Tyr. Ion-exchange chromatography was used to purify immunoglobulins, in order to improve the specificity in measurement of I2Tyr-I2Tyr level in patient serum. IgG binding capacity versus I2Tyr-I2Tyr was considerably increased after immunoglobulin purification.Acknowledgments. The authors with to thank Mrs M. Ollier for her valuable technical assistance. 相似文献