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1.
In a hybrid instrument under minimal multiple-collision conditions, the collision-induced fragmentation of the [M + H]+ ions of tetraalanine and tetraglycine are dominated by the gamma 2 fragment, in distinction to the fragmentation of the [M + H]+ ions of hexa- and octaalanine and -glycine; these latter fragmentations are instead a distribution of b and y ions, and to a lesser extent a ions. This difference may be rationalized on the basis of control of the fragmentation by the most basic site in the peptide, which may be identified by taking internal hydrogen bonding into account. On increasing the collision energy from 10 to 150 eV, a, b and y ions of lower mass appear; and in several cases a peak due to a smaller b ion becomes the base peak. The ion distribution in the spectra of these protonated peptides serves as a baseline from which the effects of conformation on side-group rearrangements and other fragmentations may be explored. 相似文献
2.
M. Nagayama O. Takaoka K. Inomata Y. Yamagata 《Origins of life and evolution of the biosphere》1990,20(3-4):249-257
Though diketopiperazines (DKP) are formed in most experiments concerning the prebiotic peptide formation, the molecules have not been paid attention in the studies of chemical evolution. We have found that triglycine, tetraglycine or pentaglycine are formed in aqueous solution of glycine anhydride (DKP) and glycine, diglycine or triglycine, respectively. A reaction of alanine with DKP resulted in the formation of glycylglycylalanine under the same conditions. These results indicate that the formation of the peptide bonds proceeds through the nucleophilic attack of an amino group of the amino acids or the oligoglycines on the DKP accompanied by the ring-opening.The formation of glycine anhydride, di-, tri- and tetraglycine was also observed in a mixed aqueous solution of urea and glycine in an open system to allow the evaporation of ammonia. A probable pathway is proposed for prebiotic peptide formation through diketopiperazine on the primitive Earth. 相似文献
3.
Hermann E. Bleich J.D. Cutnell A.R. Day R.J. Freer Jay A. Glasel J.F. McKelvy 《Biochemical and biophysical research communications》1976,71(1):168-174
Using proton spin-lattice relaxation times, the interaction of small oligopeptides with sonicated vesicles of synthetic β-γ-dimyristoyl L-α-lecithin has been monitored at 29°C in D2O. The measured relaxation times for the lecithin choline methyl, alkyl chain, and terminal methyl protons were observed to shorten markedly with increasing concentration of peptide, the relaxation remaining exponential. Noticeable resonance broadening was observed at the highest peptide concentration studied. The data reported are for the effect of the pharmacologically active pentapeptide methionine-enkephalin. Similar results have been observed for the effect of tetraglycine. The relaxation of the observable resonances of the added peptide appear to be unaffected. The results are discussed in terms of peptide-vesicle interactions. 相似文献
4.
Guan R Brown PH Swaminathan CP Roychowdhury A Boons GJ Mariuzza RA 《Protein science : a publication of the Protein Society》2006,15(5):1199-1206
Peptidoglycan recognition proteins (PGRPs) are pattern recognition receptors of the innate immune system that bind bacterial peptidoglycans (PGNs). We determined the crystal structure, to 2.1 A resolution, of the C-terminal PGN-binding domain of human PGRP-I alpha in complex with a muramyl pentapeptide (MPP) from Gram-positive bacteria containing a complete peptide stem (L-Ala-D-isoGln-L-Lys-D-Ala-D-Ala). The structure reveals important features not observed previously in the complex between PGRP-I alpha and a muramyl tripeptide lacking D-Ala at stem positions 4 and 5. Most notable are ligand-induced structural rearrangements in the PGN-binding site that are essential for entry of the C-terminal portion of the peptide stem and for locking MPP in the binding groove. We propose that similar structural rearrangements to accommodate the PGN stem likely characterize many PGRPs, both mammalian and insect. 相似文献
5.
A variety of proteins, including glycosylasparaginase, have recently been found to activate functions by self-catalyzed peptide bond rearrangements from single-chain precursors. Here we present the 1.9 A crystal structures of glycosylasparaginase precursors that are able to autoproteolyze via an N --> O acyl shift. Several conserved residues are aligned around the scissile peptide bond that is in a highly strained trans peptide bond configuration. The structure illustrates how a nucleophilic side chain may attack the scissile peptide bond at the immediate upstream backbone carbonyl and provides an understanding of the structural basis for peptide bond cleavage via an N --> O or N --> S acyl shift that is used by various groups of intramolecular autoprocessing proteins. 相似文献
6.
De novo designed peptide based super secondary structures are expected to provide scaffolds for the incorporation of functional sites as in proteins. Self-association of peptide helices of similar screw sense, mediated by weak interactions, has been probed by the crystal structure determination of two closely related peptides: Ac-Gly1-Ala2-Delta Phe3-Leu4-Val5-DeltaPhe6-Leu7-Val8-DeltaPhe9-Ala10-Gly11-NH2 (I) and Ac-Gly1-Ala2-DeltaPhe3-Leu4-Ala5-DeltaPhe6-Leu7-Ala8-DeltaPhe9-Ala10-Gly11-NH2 (II). The crystal structures determined to atomic resolution and refined to R factors 8.12 and 4.01%, respectively, reveal right-handed 3(10)-helical conformations for both peptides. CD has also revealed the preferential formation of right-handed 3(10)-helical conformations for both molecules. Our aim was to critically analyze the packing of the helices in the solid state with a view to elicit clues for the design of super secondary structural motifs such as two, three, and four helical bundles based on helix-helix interactions. An important finding is that a packing motif could be identified common to both the structures, in which a given peptide helix is surrounded by six other helices reminiscent of transmembrane seven helical bundles. The outer helices are oriented either parallel or antiparallel to the central helix. The helices interact laterally through a combination of N--H...O, C--H...O, and C--H...pi hydrogen bonds. Layers of interacting leucine residues are seen in both peptide crystal structures. The packing of the peptide helices in the solid state appears to provide valuable leads for the design of super secondary structural modules such as two, three, or four helix bundles by connecting adjacent antiparallel helices through suitable linkers such as tetraglycine segments. 相似文献
7.
Luisa Ronga Pasquale Palladino Gabriella Saviano Teodorico Tancredi Ettore Benedetti Raffaele Ragone Filomena Rossi 《Journal of peptide science》2008,14(10):1096-1102
The 173–195 segment corresponding to the helix 2 of the globular PrP domain is a good candidate to be one of the several ‘spots’ of intrinsic structural flexibility, which might induce local destabilization and concur to protein transformation, leading to aggregation‐prone conformations. Here, we report CD and NMR studies on the α2‐helix‐derived peptide of maximal length (hPrP[180–195]) that is able to exhibit a regular structure different from the prevalently random arrangement of other α2‐helix‐derived peptides. This peptide, which has previously been shown to be affected by buffer composition via the ion charge density dependence typical of Hofmeister effects, corresponds to the C‐terminal sequence of the PrPC full‐length α2‐helix and includes the highly conserved threonine‐rich 188–195 segment. At neutral pH, its conformation is dominated by β‐type contributions, which only very strong environmental modifications are able to modify. On TFE addition, an increase of α‐helical content can be observed, but a fully helical conformation is only obtained in neat TFE. However, linking of the 173–179 segment, as occurring in wild‐type and mutant peptides corresponding to the full‐length α2‐helix, perturbs these intrinsic structural propensities in a manner that depends on whether the environment is water or TFE. Overall, these results confirm that the 180–195 parental region in hPrPC makes a strong contribution to the chameleon conformational behavior of the segment corresponding to the full‐length α2‐helix, and could play a role in determining structural rearrangements of the entire globular domain. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
8.
The ability of biological ion channels to conduct selected ions across cell membranes is critical for the survival of both animal and bacterial cells. Numerous investigations of ion selectivity have been conducted over more than 50 years, yet the mechanisms whereby the channels select certain ions and reject others are not well understood. Here we report a new application of Jarzynski’s Equality to investigate the mechanism of ion selectivity using non-equilibrium molecular dynamics simulations of Na+ and K+ ions moving through the KcsA channel. The simulations show that the selectivity filter of KcsA adapts and responds to the presence of the ions with structural rearrangements that are different for Na+ and K+. These structural rearrangements facilitate entry of K+ ions into the selectivity filter and permeation through the channel, and rejection of Na+ ions. A mechanistic model of ion selectivity by this channel based on the results of the simulations relates the structural rearrangement of the selectivity filter to the differential dehydration of ions and multiple-ion occupancy and describes a mechanism to efficiently select and conduct K+. Estimates of the K+/Na+ selectivity ratio and steady state ion conductance for KcsA from the simulations are in good quantitative agreement with experimental measurements. This model also accurately describes experimental observations of channel block by cytoplasmic Na+ ions, the “punch through” relief of channel block by cytoplasmic positive voltages, and is consistent with the knock-on mechanism of ion permeation. 相似文献
9.
Tigran V. Chalikian Armen P. Sarvazyan Theodor Funck Kenneth J. Breslauer 《Biopolymers》1994,34(4):541-553
We have determined the partial molar volumes, expansibilities, and adiabatic compressibilities of glycine, diglycine, triglycine, tetraglycine, and pentaglycine over the temperature range 18–55°C. These data were analyzed and interpreted in terms of the hydration of these short oligoglycines and their constituent groups. From our results, we have estimated the contributions of the peptide group to the partial molar volume and the partial molar adiabatic compressibility of these oligoglycines. Based on these data, we propose that each of the polar atomic groups of the peptide bond forms approximately two hydrogen bonds with adjacent water molecules. Furthermore, the temperature dependence of the partial molar volume suggests that water that solvates the polar groups of a peptide linkage behaves more like a “normal” liquid than does bulk water, which exhibits its well-known anomalous liquid properties. © 1994 John Wiley & Sons, Inc. 相似文献
10.
Rudresh Ramakumar S Ramagopal UA Inai Y Goel S Sahal D Chauhan VS 《Structure (London, England : 1993)》2004,12(3):389-396
De novo design of supersecondary structures is expected to provide useful molecular frameworks for the incorporation of functional sites as in proteins. A 21 residue long, dehydrophenylalanine-containing peptide has been de novo designed and its crystal structure determined. The apolar peptide folds into a helical hairpin supersecondary structure with two right-handed helices, connected by a tetraglycine linker. The helices of the hairpin interact with each other through a combination of C-H.O and N-H.O hydrogen bonds. The folding of the apolar peptide has been realized without the help of either metal ions or disulphide bonds. A remarkable feature of the peptide is the unanticipated occurrence of an anion binding motif in the linker region, strikingly similar in conformation and function to the "nest" motif seen in several proteins. The observation supports the view for the possible emergence of rudimentary functions over short sequence stretches in the early peptides under prebiotic conditions. 相似文献
11.
Pullen R. A. Jenkins J. A. Tickle I. J. Wood S. P. Blundell T. L. 《Molecular and cellular biochemistry》1975,7(1):5-17
Summary This study is concerned with nondenaturational structural rearrangements of proteins in solution under the influence of physiologically moderate temperatures and salts.Temperature-induced rearrangements are viewed as the reason for breaks in Arrhenius curves of the enzymatic activity. In the cytosol as well as in biological membranes, proteins remain conformationally labile and participate in cooperative structural transitions of membranes. Such transitions are initiated by physiologically moderate temperatures, hormones, salts and aminoacids and affect the functional activity of cell membranes. It is suggested that structural lability of proteins and membranes is of importance in metabolic regulation.It may be said without any exaggeration that a basic objective of biochemistry and biophysics is to find the mechanisms by which coordination of numerous chemical and physicochemical processes along with adaptation to a changing environment can be regulated by the cell. An analysis of a large body of accumulated material and information on this subject leads us to a simple idea; namely, that metabolism is regulated primarily through weak physicochemical interactions. It is weak bonds arising at the sites of contact between effector and regulated macromolecules which serve as a trigger for the regulatory mechanisms of various types. This principle is fundamental for the long range mechanism and for the short-range cytoplasmic allosteric enzyme regulation. In each regulatory act of this type the regulated macromolecule undergoes conformational transition between the states of different functional activity.It is generally recognized1,2 that in most cases conformational transition is cooperative by nature. However, biopolymers in a cell are an integral part of compact and orderly membraneous phases with active intermolecular interactions. Therefore it is pertinent to inquire whether the elementary act of regulation is necessarily always restricted to one macromolecule or whether there is a possibility of functionally important cooperative transition involving most if not all components of a polymolecular ensembles. We have in mind here the structural long-range effects when local perturbations in the receptor region of the membrane are able to propagate their effects to comparatively large distances. This would occur in a stepwise cooperative transition between two discrete structural states. After we expressed this idea3,4 we discovered that there had been earlier opinions along such lines5 and in recent years similar views have become widely known6,7,8.Since 1965 our laboratory has been concerned with experimental development of a hypothesis of the membraneous-cooperative-conformational mechanism in the regulation of life processes. We have taken the following path: nondenaturational conformational transitions of proteins in solution rearrangements at the isolated membrane level rearrangements in the intact membrane system of the cells.an invited article. 相似文献
12.
V. N. Uversky S. E. Permyakov I. I. Senin A. M. Cherskaya S. V. Shulga-Morskoy D. V. Zinchenko A. M. Alekseev A. A. Zargarov V. M. Lipkin P. P. Philippov E. A. Permyakov 《Russian Journal of Bioorganic Chemistry》2000,26(3):152-156
The structural properties of myristoylated forms of recombinant recoverin of the wild type and of its mutants with damaged
second and/or third Ca2+-binding sites were studied by fluorimetry and circular dichroism. The interaction of wild-type recoverin with calcium ions
was shown to induce unusual structural rearrangements in its molecule. In particular, protein binding with Ca2+ ions results in an increase in the mobility of the environment of Trp residues, in hydrophobicity, and in thermal stability
(its thermal transition shifts by 15°C to higher temperatures) but has almost no effect on its secondary structure. Similar
structural changes induced by Ca2+ are also characteristic of the -EF2 mutant of recoverin whose second Ca2+-binding site is modified and cannot bind calcium ions. The structural properties of the -EF3 and -EF2,3 mutants (whose third
or simultaneously second and third Ca2+-binding sites, respectively, are modified and damaged) are practically indifferent to the presence of calcium ions.
For the communication I, see [1]. 相似文献
13.
Structural and dynamic characterization of a freestanding acyl carrier protein involved in the biosynthesis of cyclic lipopeptide antibiotics
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Subrata Paul Hiroaki Ishida Leonard T. Nguyen Zhihong Liu Hans J. Vogel 《Protein science : a publication of the Protein Society》2017,26(5):946-959
Friulimicin is a cyclic lipodecapeptide antibiotic that is produced by Actinoplanes friuliensis. Similar to the related lipopeptide drug daptomycin, the peptide skeleton of friulimicin is synthesized by a large multienzyme nonribosomal peptide synthetase (NRPS) system. The LipD protein plays a major role in the acylation reaction of friulimicin. The attachment of the fatty acid group promotes its antibiotic activity. Phylogenetic analysis reveals that LipD is most closely related to other freestanding acyl carrier proteins (ACPs), for which the genes are located near to NRPS gene clusters. Here, we report that the solution NMR structure of apo‐LipD is very similar to other four‐helix bundle forming ACPs from fatty acid synthase (FAS), polyketide synthase, and NRPS systems. By recording NMR dynamics data, we found that the backbone motions in holo‐LipD are more restricted than in apo‐LipD due to the attachment of phosphopantetheine moiety. This enhanced stability of holo‐LipD was also observed in differential scanning calorimetry experiments. Furthermore, we demonstrate that, unlike several other ACPs, the folding of LipD does not depend on the presence of divalent cations, although the presence of Mg2+ or Ca2+ can increase the protein stability. We propose that small structural rearrangements in the tertiary structure of holo‐LipD which lead to the enhanced stability are important for the cognate enzyme recognition for the acylation reaction. Our results also highlight the different surface charges of LipD and FAS‐ACP from A. friuliensis that would allow the acyl‐CoA ligase to interact preferentially with the LipD instead of binding to the FAS‐ACP. 相似文献
14.
P. E. Conen 《CMAJ》1967,96(25):1599-1605
This review discusses the significance of chromosomal abnormalities found in leukemia with the bias of belief that these have a primary role or are the mechanism of action of leukemogenic agents. The Philadelphia chromosome (Ph1) is present in marrow cells examined without culture at any stage of most patients with chronic granulocytic leukemia (CGL). the presence of this chromosome is of diagnostic and prognostic value.Varied chromosomal abnormalities have been found in acute leukemia. Each abnormality, which may be unique, is absent in remission, found again at relapse and is seldom changed by therapy. Abnormalities may be of number of chromosomes (aneuploid) or structural rearrangements resulting in “marker” chromosomes, Ranges of abnormal numbers of chromosomes, when present, usually have related patterns which suggest origin of several cell types from one initial cell. Cells from patients with increased risk of leukemia owing to genetic factors have a high incidence of chromosome breakage and structural rearrangements suggesting a mechanism for production of clones of abnormal, possibly leukemic, cells. 相似文献
15.
Normal vibration analysis of cyclic tetraglycine has been carried out employing the Urey-Bradley force field and the vibrational assignments are compared with those in related molecules. 相似文献
16.
Gianni S Walma T Arcovito A Calosci N Bellelli A Engström A Travaglini-Allocatelli C Brunori M Jemth P Vuister GW 《Structure (London, England : 1993)》2006,14(12):1801-1809
Understanding the basis of communication within protein domains is a major challenge in structural biology. We present structural and dynamical evidence for allosteric effects in a PDZ domain, PDZ2 from the tyrosine phosphatase PTP-BL, upon binding to a target peptide. The NMR structures of its free and peptide-bound states differ in the orientation of helix alpha2 with respect to the remainder of the molecule, concomitant with a readjustment of the hydrophobic core. Using an ultrafast mixing instrument, we detected a deviation from simple bimolecular kinetics for the association with peptide that is consistent with a rate-limiting conformational change in the protein (k(obs) approximately 7 x 10(3) s(-1)) and an induced-fit model. Furthermore, the binding kinetics of 15 mutants revealed that binding is regulated by long-range interactions, which can be correlated with the structural rearrangements resulting from peptide binding. The homologous protein PSD-95 PDZ3 did not display a similar ligand-induced conformational change. 相似文献
17.
It is shown that real-time 2D solid-state NMR can be used to obtain kinetic and structural information about the process of
protein aggregation. In addition to the incorporation of kinetic information involving intermediate states, this approach
can offer atom-specific resolution for all detectable species. The analysis was carried out using experimental data obtained
during aggregation of the 10.4 kDa Crh protein, which has been shown to involve a partially unfolded intermediate state prior
to aggregation. Based on a single real-time 2D 13C–13C transition spectrum, kinetic information about the refolding and aggregation step could be extracted. In addition, structural
rearrangements associated with refolding are estimated and several different aggregation scenarios were compared to the experimental
data. 相似文献
18.
Previous studies showed that binding of water-soluble phosphatidylserine (C6PS) to bovine factor Xa (FXa) leads to Ca2+-dependent dimerization in solution. We report the effects of Ca2+, C6PS, and dimerization on the activity and structure of human and bovine FXa. Both human and bovine dimers are 106- to 107-fold less active toward prothrombin than the monomer, with the decrease being attributed mainly to a substantial decrease in kcat. Dimerization appears not to block the active site, since amidolytic activity toward a synthetic substrate is largely unaffected. Circular dichroism reveals a substantial change in tertiary or quaternary structure with a concomitant decrease in α-helix upon dimerization. Mass spectrometry identifies a lysine (K270) in the catalytic domain that appears to be buried at the dimer interface and is part of a synthetic peptide sequence reported to interfere with factor Va (FVa) binding. C6PS binding exposes K351 (part of a reported FVa binding region), K242 (adjacent to the catalytic triad), and K420 (part of a substrate exosite). We interpret our results to mean that C6PS-induced dimerization produces substantial conformational changes or domain rearrangements such that structural data on PS-activated FXa is required to understand the structure of the FXa dimer or the FXa-FVa complex. 相似文献
19.
Moses Julia P. Inayathullah N. Mohammed Murugesan Muthu Andrews Maneesha E. Balasubramanian M. P. Jayakumar Rajadas 《International journal of peptide research and therapeutics》2003,10(1):25-32
Summary Conductometry, circular dichroism and fluorescence spectroscopy are the techniques employed to investigate the effect of added
calcium ions and other monovalent and divalent metal ions on aqueous solutions of nonionic peptide aggregates, Boc-Leu-Asn-OEt
(1). It is observed that among all the metal ions studied, Ca2+ ions facilitate the aggregation of the peptide. The interior dielectric constant of the micelles (ε) was found to depend
upon the proportion of Ca2+ complexed peptide with the peptide mononers in the micelles. When Ca2+ ion becomes 1/4th of the peptide concentration, there is a structural transition leading to drastic change in the interior
of the micro dielectric constant (ɛ
m). 相似文献