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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The primary structure of pancreatic ribonuclease of the superspecies Spalax leucodon has been determined. Only one difference with the previously determined sequence of the superspecies Spalax ehrenbergi was detected; the proline residue at position 42 has been replaced by alanine. Proline-42 is a well-conserved residue in mammalian pancreatic ribonucleases; the only other species with alanine at this position is the three-toed sloth. As the Muridae and the Spalacidae diverged 20-40 million years ago and the superspecies S. leucodon and S. ehrenbergi about 1-2 million years ago, and as pancreatic ribonuclease exhibits 24 substitutions in the line from the Muridae/Spalacidae ancestor to Spalax, a difference of one amino residue between the sequences of the two Spalax superspecies is what may be expected.
Mol Phylogenet Evol 1993 Sep
PMID:The primary structure of pancreatic ribonuclease from mole rat superspecies Spalax leucodon. 813 26

Proline residues confer unique structural constraints on peptide chains and markedly influence the susceptibility of proximal peptide bonds to protease activity. This review presents a critical analysis of peptidases involved in the cleavage of proline-containing peptide bonds, with particular attention to the role of proline peptidases in the regulation of the lifetime of biologically active peptides. Peptidases discussed include aminopeptidase P, prolidase, dipeptidyl peptidase IV, prolyl endopeptidase, and prolyl iminopeptidase. Attention is also given to HIV-1 protease, because this key enzyme processes an Xaa-Pro peptide bond. Analysis of the above enzymes reveals that they may function as key pacemakers in the control of the activity of many peptide hormones and that they are involved in a variety of immunological processes, including T-cell-mediated immune response. The novel occurrence of cis-trans isomerization about Xaa-Pro bonds and the biological function of peptidyl-prolyl cis-trans isomerases (immunophilins) are reviewed.
Crit Rev Biochem Mol Biol 1993
PMID:Proline-dependent structural and biological properties of peptides and proteins. 844 42

Leishmania major promastigotes maintain a relatively high pool of free amino acids (> 100 mM) under in vitro growth conditions. They also maintain a hyperpolarized plasma membrane which is primarily set by a dicyclohexylcarbodiimide (DCCD)-sensitive electrogenic H(+)-pump. We studied here the possible contribution of the membrane potential (Vm) and the transmembrane proton gradient (delta pH) to the mediated uptake of amino acids and their intracellular accumulation. Proline transport and accumulation were assessed by analysis of time-dependent changes in the internal pools of free amino acids and by uptake of radiolabelled proline. Proline uptake was markedly affected by changes in the Vm and considerably less by changes in delta pH. The most pronounced effects were obtained by treatment with either the H(+)-uncoupler carbonylcyanide chlorophenylhydrazone (CCCP), the cation ionophore gramicidin or by omitting Cl- from the medium (by exchange with gluconate or mannitol). Relatively smaller effects were obtained in the presence of the H(+)-ATPase inhibitor DCCD or with the anion transport blocker 4,4'-diisothiocyanodihydrostilbene-2,2'-disulfonic acid (H2DIDS). No significant effects were found with cells exposed to K+ in the presence of nigericin, to Na+ in the presence of monensin or to other cations substituting for Na+. These results suggest that neither extracellular Na+ or K+, per se, nor even intracellular pH, play a major role in proline uptake and accumulation. A significant stimulation in proline uptake induced by HCO3- could be associated with membrane hyperpolarization or intracellular alkalinization. The present observations indicate that uphill nutrient uptake by Leishmania promastigotes is largely determined by Vm. The relatively high intracellular pools of amino acids might be of physiological relevance to osmoregulation by parasites.
Mol Biochem Parasitol 1995 Dec
PMID:Amino acid uptake and intracellular accumulation in Leishmania major promastigotes are largely determined by an H(+)-pump generated membrane potential. 872 Jan 71

Proline is highly conserved in the presumed transmembrane alpha-helices of seven-transmembrane helix-containing, G protein coupled receptors. Unique properties of this imino acid have led to speculations of structural and perhaps dynamic importance for seven-transmembrane helix-containing receptor function. To avoid potentially deleterious consequences of proline-directed mutagenesis, substitutions were made in the X residue of X-Pro peptide bonds (where X is the residue on the amino-terminal side of proline), which may influence static geometries and potential agonist-induced conformational changes at the X-Pro peptide bond. In the fifth helix, Ile205 was substituted with either an alanine (I205A) or a tyrosine (I205Y). Similarly, in the sixth helix, Leu286 was substituted with either an alanine (L286A) or a tyrosine (L286Y). Mutant I205A demonstrated subtle changes in D1 pharmacology and signal transduction. The I205Y and L286Y mutations produced comparatively drastic impairments in both binding and signal transduction. Remarkably, the L286A mutation resulted in constitutive activity characterized by elevated basal signal transduction and increased agonist potencies. In addition, (R)-(+)-SCH23390, a classical antagonist at the wild-type D1 receptor, behaved as a partial agonist at L286A. This is the first report of a constitutively active receptor resulting from this point mutation and the first report of a constitutively active mutant dopamine receptor. These results are discussed in terms of binding pocket geometry and potential mechanisms of signal transduction.
Mol Pharmacol 1996 Nov
PMID:Mutagenesis of residues adjacent to transmembrane prolines alters D1 dopamine receptor binding and signal transduction. 891 66

The effect of proline on the prevention of trichloroacetic acid (TCA)-induced protein precipitation is studied. It is found that proline at high concentrations (> 4.0 M) completely prevents TCA-induced precipitation of hen egg white lysozyme. Other osmolytes such as ethylene glycol, glycerol and sucrose fail to prevent the TCA-induced precipitation of lysozyme. Viscosity and 1-anilino-8-naphthalene sulphonic acid binding experiments suggest that proline at high concentration forms an ordered supramolecular assembly. Proline is shown to increase the solubility of protein due to formation of such higher order assemblies. A model of the supra-molecular assembly of proline is proposed and a possible in vivo role of the increased levels of proline under water stress is discussed.
Biochem Mol Biol Int 1997 Feb
PMID:Proline is a protein solubilizing solute. 906 63

The role of the phytohormone abscisic acid (ABA) in the regulation of proline synthesis was investigated by following the expression of the At-P5S and At-P5R proline biosynthesis genes in Arabidopsis thaliana wild type, in an ABA-deficient aba1-1 mutant as well as in ABA-insensitive abi1-1 and abi2-1 mutants after ABA, cold and osmotic stress treatments. In wild-type and in ABA mutant seedlings, 50 microM ABA or osmotic stress treatment triggered expression of At-P5S, whereas At-P5R accumulation was scarcely detectable. Expression of either gene was mediated by endogenous ABA since transcript levels were similar in wild-type and in ABA-deficient mutant plants. Proline accumulated to a greater extent after osmotic stress than upon ABA or cold treatment. Thus, ABA-treated abi1-1 mutant plants accumulated less proline than the ABA-treated wild type. Upon salt stress, proline accumulated to a lesser extent in aba1-1 and abi1-1 mutant plants, suggesting an indirect role of ABA on proline accumulation during salt adaptation of the plant. These results indicate that the expression of the genes of the proline biosynthetic pathway is ABA independent upon cold and osmotic treatments, although their expression can be triggered by exogenously applied ABA. However, the endogenous ABA content may affect proline accumulation upon salt stress, suggesting post-transcriptional control of proline biosynthesis in response to NaCl.
Mol Gen Genet 1997 Mar 18
PMID:Abscisic acid-independent and abscisic acid-dependent regulation of proline biosynthesis following cold and osmotic stresses in Arabidopsis thaliana. 910 97

The 26S proteasome is a 2-Megadalton proteolytic complex with over 30 distinct subunits. The 19S particle, a subcomplex of the 26S proteasome, is thought to confer ATP-dependence and ubiquitin-dependence on the proteolytic core particle of the proteasome. Given the complexity of the 19S particle, genetic approaches are likely to play an important role in its analysis. We have initiated biochemical and genetic studies of the 19S particle in Saccharomyces cerevisiae. Here we describe the localization to the proteasome of several ATPases that were previously proposed to be involved in transcription. Independent studies indicate that the mammalian 26S proteasome contains closely related ATPases. We have also found that the multiubiquitin chain binding protein Mcb1, a homolog of the mammalian S5a protein, is a subunit of the yeast proteasome. However, contrary to expectation, MCB1 is not an essential gene in yeast. The mcb1 mutant grows at a nearly wild-type rate, and the breakdown of most ubiquitin-protein conjugates is unaffected in this strain. One substrate, Ub-Proline-beta gal, was found to require MCB1 for its breakdown, but it remains unclear whether Mcb1 serves as a ubiquitin receptor in this process. Our data suggest that the recognition of ubiquitin conjugates by the proteasome is a complex process which must involve proteins other than Mcb1.
Mol Biol Rep 1997 Mar
PMID:ATPase and ubiquitin-binding proteins of the yeast proteasome. 922 76

Peptidyl-prolyl cis/trans isomerisation has been frequently found as a rate limiting step in the folding of proteins. In order to determine whether the nature of the amino acid preceding proline controls the probability of cis prolyl bonds in native proteins, systematic studies on the thermodynamics and kinetics of the prolyl isomerisation in the pentapeptide series Ac-Ala-Xaa-Pro-Ala-Lys-NH2 were performed. All proteinogenic amino acids were substituted in the position preceding proline. When measured by 1H-NMR and CD spectroscopy both isomers proved to be devoid of ordered structure in the whole series of the oligopeptides in aqueous solution. Thus, isomerization rates and cis/trans ratios calculated from solvent jump and 1H-NMR magnetisation transfer experiments exclusively reflect the side-chain effects of the Xaa position in the peptide series. There is a rough correlation between the cis content in the oligopeptides and the propensity of Xaa-Pro cis prolyl bonds in proteins. This correlation suggests that the prolyl bond conformation is mainly determined by local effects in proteins. The rate constants kc-->t of pentapeptides containing unionised amino acids preceding proline range from 3.2 x 10(-3) s-1 (Xaa = Ala) to 0.5 x 10(-3) s-1 (Xaa = Trp) at 4 degrees C. Proline clustering led to an isomerisation cycle indicating considerable influence on the isomerisation rates of the peptide bond conformations flanking the rotating bond. Both tyrosine and histidine specifically reduce isomerisation rates severalfold by deprotonation of their respective side-chains.
J Mol Biol 1998 Jun 05
PMID:Side-chain effects on peptidyl-prolyl cis/trans isomerisation. 964 49

Significant betaine aldehyde dehydrogenase activity was found in porcine kidney. The enzyme was purified 320-fold with an overall recovery of 11%. It had a specific activity of 115.8 nkats/mg protein and proved to be homogeneous by SDS-PAGE with a subunit molecular mass of 52 kDa. IEF studies showed three bands with pI values of 5.74, 5.68 and 5.58, respectively. The enzyme was stable in a pH range between 5.0 and 10.0 and the optimum pH was 9.5. The reaction is highly specific for NAD+ and betaine aldehyde, although acetaldehyde, butyraldehyde and glyceraldehyde can be used. Estimated values of Km at pH 8.0 and 25 degrees C were 127 microM for betaine aldehyde and 40 microM for NAD+. The reaction could not be reversed even at high glycine betaine concentrations. The enzyme was not activated by salts at high concentrations but it was salt tolerant-retaining 50% of maximal activity at 1.0 M K+ and Na+. It is inferred that salt tolerance is an essential property for an enzyme participating in the cellular synthesis of an osmoprotectant. Proline, glycerol, sucrose and mannitol had a little effect on the enzyme activity while glycine betaine had an inhibitory effect.
Comp Biochem Physiol B Biochem Mol Biol 1998 Mar
PMID:Porcine kidney betaine aldehyde dehydrogenase: purification and properties. 973 33

Proline effectively inhibits protein aggregation during the refolding of bovine carbonic anhydrase. Other osmolytes used such as glycine and ethylene glycol fail to exhibit the 'aggregation-blockade' role shown by proline. Results of viscosity and ANS fluorescence (1-anilino-8-naphthalene sulphonic acid) experiments suggest that proline at high concentrations forms an ordered supramolecular assembly. Based on these results, it is proposed that proline behaves as a protein folding chaperone due to the formation of an ordered, amphipathic supramolecular assembly. To our knowledge, this is the first report wherein proline is proposed as a protein folding aid.
Biochem Mol Biol Int 1998 Oct
PMID:The role of proline in the prevention of aggregation during protein folding in vitro. 981 90


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