Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT00572 (Asn)
 11,732 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glycopeptides containing mainly four amino acid residues in the sequence Asn-Leu-Thr-Ser, with small amounts of additional amino acid residues, were isolated from enzymic hydrolysates of hen's-egg albumin. Heterogeneity of the carbohydrate moiety was confirmed. Acid-base titrations showed that the alpha-amino group has a pKa value of 6.43 at 25 degrees C. The standard free engery and entropy changes associated with the ionization at 25 degrees C were 37.2kJ-mol-1 and -0.014kJ-mol-1- K-1 respectively. The complications arising in the interpretation of titration curves of the glycopeptides, which are heterogeneous with respect to the peptide chain, were considered and discussed in the light of the earlier suggestion that the titration curve of the glycopeptide might be interpreted as being due in part to a structure in which the hydroxyl group of the threonine residue is hydrogen-bonded to the beta-aspartamido oxygen atom [Neuberger & Marshall (1968) in Symposium on Foods - Carbohydrates and their Roles (Schultz, H.W., Cain, R.F. & Wrolstad, R.W., eds.), pp. 115-132, Avi Publishing Co., Westport, CT]. It is concluded that either the glycopeptides do not contain a hydrogen bond of that type, or, if they do, that it cannot be recognized by acid-base-titration studies.
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PMID:Acid dissociation constants of glycopeptides. 1 94

The effect of ring substituents on the rates of deacylation of 8 meta- and para-substituted benzoyl papains was evaluated. The rate constants were found to depend upon a single ionizing group of pKa = 4.2--4.3, and to decrease by a factor of approximately 2.2 when measured in 94% D2O/H2O. The rates of deacylation are increased greatly by electron-withdrawing groups on the benzene ring. The Hammett rho value is 2.74 +/- 0.32. A plot of the rate constants for deacylation of the benzoyl papains against the corresponding constants for substituted benzoyl chymotrypsins generates a straight line of slope 1.0. This result suggests a very similar distribution of charge on the benzoyl moiety in the transition state for the two enzymes, which is interpreted in terms of the net charge of the transition state for the deacylation of nonspecific acyl papains being equal to--1 with the general base catalyzed assistance to the attack of water on the acyl enzyme being provided by the negatively charged Asp-158 rather than by the neutral Asn-175-His-159 hydrogen bond network. This result together with a survey of literature data suggests that the role of Asp-158 in papain catalysis has been underestimated. The evidence advanced to date in support of the proposition that an imidazolium-159-cysteine-25 thiolate ion pair exists in native papain is evaluated and considered to be insufficient to decide the issue.
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PMID:Effects of substituents on the rates of deacylation of substituted benzoyl papains. Role of a carboxylate residue in the catalytic mechanism. 2 48

The construction of molecular models for the human serotransferrin glycans shows that they present one compact section linked to the protein and constituted by the pentasaccharide alpha-Man-(1 leads to 3)-[alpha-Man-(1 leads to 6)]-beta-Man-(1 leads to 4)-beta-GlcNAc-(1 leads to 4)-beta-GlcNAc-(1 leads to)-Asn to which are attached two "antennae" consisting of the trisaccharide alpha-NANA-(2 leads to 6)-beta-Gal-(1 leads to 4)-beta-GlcNAc. The trisaccharide sequence beta-Man-(1 leads to 4)-beta-GlcNAc-(1 leads to 4)-beta-GlcNAc adopts a flat and rigid conformation, stabilised by hydrogen bonds. In contrast, the sequence alpha-NANA-(1 leads to 6)-beta-Gal-(1 leads to 4)-beta-GlcNAc-(1 leads to 2)-alpha-Man takes up a helical configuration. The two "antennae" can be disposed on the pentasaccharide core to give two possible configurations, one Y-shaped and the other T-shaped. In both cases, the general conformation of the glycans is perfectly compatible with their postulated role as a recognition signal.
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PMID:[Spatial conformation of human serotransferrin glycans]. 10 56

Calculated probabilities of bend formation in 47 amino acid sequences of N-acetyl-N'-methylamide dipeptides, determined from a statistical mechanical analysis using empirical conformational energies, were compared with the observed fraction of bends formed in the same 47 dipeptide sequences in the x-ray structures of 20 globular proteins. Agreement between the calculated and observed fraction of bends was found for 26 dipeptides, suggesting that, for those particular dipeptide sequences, local interactions dominate over long-range interactions in determining conformational preference. Seven dipeptide sequences, all of which contained a Gly residue, had a significantly higher calculated than observed bend preference, indicating the strong influence of long-range and/or solvent interactions in those sequences. Of the 14 sequences for which the calculated was significantly less than the observed bend fraction, 13 dipeptide sequences contained at least one polar residue (Ser, Asn, or Asp) and/or an aromatic residue (Phe or Tyr), suggesting that solvent effects may play an important role in dictating the conformation in these sequences. The analysis of dipeptide sequences in the twenty globular proteins also indicated that the 4 leads to 1 hydrogen bond is not a dominant factor in stabilizing bends in proteins, and that most dipeptide sequences are capable of forming several types of bend conformations.
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PMID:Local interactions in bends of proteins. 27 Jun 58

Red kangaroo (Macropus rufus) ribonuclease was isolated from pancreatic tissue by affinity chromatography. The amino acid sequence was determined by automatic sequencing of overlapping large fragments and by analysis of shorter peptides obtained by digestion with a number of proteolytic enzymes. The polypeptide chain consists of 122 amino acid residues. Compared to other ribonucleases, the N-terminal residue and residue 114 are deleted. In other pancreatic ribonucleases position 114 is occupied by a cis proline residue in an external loop at the surface of the molecule. Other remarkable substitutions are the presence of a tyrosine residue at position 123 instead of a serine which forms a hydrogen bond with the pyrimidine ring of a nucleotide substrate, and a number of hydrophobichydrophilic interchanges in the sequence 51-55, which forms part of an alpha-helix in bovine ribonuclease and exhibits few substitutions in the placental mammals. Kangaroo ribonuclease contains no carbohydrate, although the enzyme possesses a recognition site for carbohydrate attachment in the sequence Asn-Val-Thr (62-64). The enzyme differs at about 35-40% of the positions from all other mammalian pancreatic ribonucleases sequenced to date, which is in agreement with the early divergence between the marsupials and the placental mammals. From fragmentary data a tentative sequence of red-necked wallaby (Macropus rufogriseus) pancreatic ribonuclease has been derived. Eight differences with the kangaroo sequence were found.
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PMID:The amino-acid sequence of kangaroo pancreatic ribonuclease. 65 39

The sequence analysis of llama (Lama glama, Camelidae) hemoglobin is described. The chains were separated, cleaved by trypsin as previously described, quantitatively characterized and sequenced in the sequenator. The llama hemoglobin differs from the human hemoglobin in that it has 25 different amino acids in the alpha chain and 24 different amino acids in the beta chain. The interaction between protein and phosphate is discussed. The earlier finding that the O2 affinity of the llama hemoglobin is dependent on its content of 2, 3-bisphosphoglycerate is interpreted here as a mutation of the 2, 3-bisphosphoglycerate contact position beta2 His in human hemoglobin to beta2 Asn in llama hemoglobin, whereby one of the four 2, 3-bisphosphoglycerate contact points is interrupted. This interruption gives rise to a diminished reduction of intrinsic oxygen affinity in the hemoglobin molecule and explains, on a molecular basis, the increased oxygen affinity of the llama hemoglobin, and consequently, the high-altitude respiration of the llama. By analogy, the increased O2 affinity of human fetal hemoglobin is interpreted according to previous physiological investigations on blood and fetal hemoglobin by the inactivation of the phosphoglycerate contact point beta143 His in the adult hemoglobin by mutation to gamma 143 Ser in the fetal hemoglobin. With respect to respiration in horses (2, 3-bisphosphoglycerate contact beta2 Gln), measurement of atomic parameters show that the amido group of the glutamine is situated close enough to the 2, 3-bisphosphoglycerate oxygen to build a hydrogen bond with the phosphate. Consequently, the explanation of the low-altitude respiration of the horse lies in the fact that glutamine and histidine fulfill sterochemically an identical function.
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PMID:[The interaction between phosphate and protein, and the respiration of the llama, the human fetus and the horse (author's transl)]. 66 74

A model for stereospecific complex between a polynucleotide double helix and a twisted beta-ribbon type polypeptide is described. The beta ribbon lies in the major groove with alternate side chains pointing toward the interior of the groove. The base-amino acid complementarities are: Arg, G and Asn or Gln, A. It is shown that this complex can: (a) distinguish between G and A in homopolar sequences; (b) the complex is stabilized by approx. 6 Kcal/mole per hydrogen bond per base pair; (c) the required backbone conformation is in the permitted range of Ramachandran plots.
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PMID:Elements of a DNA-polypeptide recognition code: electrostatic potential around the double helix, and a stereospecific model for purine recognition. 90 6

The COOH-terminal tetradecapeptide of ribonuclease A, Glu-Gly-Asn-Pro-Tyr-Val-Pro-Val-His-Phe-Asp-Ala-Ser-Val, and two analogs, [Ser(Me)-123]-RNase 111-124 and [Ala-123]-RNase 111-124, were synthesized by the solid phase method and were purified to chromatographic and electrophoretic homogeneity. Methods are described for the hydrolysis and quantitative amino acid analysis of peptides containing O-methylserine. The peptides were combined noncovalently with RNase 1-118 and examined for ability to regenerate enzymatic activity in the presence of the substrates C greater than p, U greater than p, poly(C) poly(U), and poly(AF). The dissociation constants of the peptide-protein complexes, and the Michaelis constants for C greater than p and U greater than p with the reconstituted enzymes were determined. The data were used to test hypotheses, drawn from x-ray crystallographic and other studies, for the role of serine-123 in the binding of substrates by ribonuclease. It was found that Ser-123- and Ala-123-containing peptides were equally active for the hydrolysis step when measured with C greater than p as substrate and for the transphosphorylation step as measured in the assays with poly(C). The serine and alanine analogs were also equally active for the transphosphorylation step when poly AF was the substrate. With U greater than p as substrate the alanine analog was 4 times less active than the serine derivative and with poly U it was 2 times less active. The semisynthetic enzyme composed of RNase 1-118 and [Ala-123]-RNase 111-124, therefore, shows appreciable selectivity for substrates containing cytosine. It was concluded that a hydrogen bond between the hydroxyl of serine-123 and the C4 amino group of cytidine or the C-7 amino group of formycin is not important for substrate binding and catalytic activity. In contrast, the hydrogen bond between the hydroxyl of serine 123 and the C-4 carbonyl oxygen of uridine contributes significantly to substrate binding and catalytic activity. The data with serine-O-methyl ether at position 123 in the tetradecapeptide were less clear because it was difficult to separate steric effects from the contributions of hydrogen bonding. Substrate binding to ribonuclease was rationalized in terms of a binding energy equivalent to a total of two hydrogen bonds per pyrimidine.
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PMID:The role of serine-123 in the activity and specificity of ribonuclease. Reactivation of ribonuclease 1-118 by the synthetic COOH-terminal tetradecapeptide, ribonuclease 111-124, and its O-methylserine and alanine analogs. 111 2

Proton nuclear magnetic resonance spectra of human hemoglobins in water reveal several exchangeable protons which are indicators of the quaternary structures of both the liganded and unliganded molecules. A comparison of the spectra of normal human adult hemoglobin with those of mutant hemoglobins Chesapeake (FG4alpha92 Arg yields Leu), Titusville (G1alpha94 Asp yields Asn), M Milwaukee (E11beta67 Val yields Glu), Malmo (FG4beta97 His yields Gln), Kempsey (G1beta99 Asp yields Asn), Yakima (G1beta99 Asp yields His), and New York (G15beta113 Val yields Glu), as well as with those of chemically modified hemoglobins Des-Arg(alpha141), Des-His(beta146), NES (on Cys-beta93)-Des-Arg(alpha141), and spin-labeled hemoglobin [Cys-beta93 reacted with N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyl)iodoacetamide], suggests that the proton in the important hydrogen bond between the tyrosine at C7alpha42 and the aspartic acid at G1beta99, which anchors the alpha1beta2 subunits of deoxyhemoglobin (a characteristic feature of the deoxy quaternary structure), is responsible for the resonance at -9.4 ppm from water at 27 degrees. Another exchangeable proton resonance which occurs at -6.4 ppm from H2O is a spectroscopic indicator of the deoxy structure. A resonance at -5.8 ppm from H2O, which is an indicator of the oxy conformation, is believed to originate from the hydrogen bond between the aspartic acid at G1alpha94 and the asparagine at G4beta102 in the alpha1beta2 subunit interface (a characteristic feature of the oxy quaternary structure). In the spectrum of methemoglobin at pH 6.2 both the -6.4- and the -5.8ppm resonances are present but not the -9.4-ppm resonance. Upon the addition of inositol hexaphosphate to methemoglobin at pH 6.2, the usual resonance at -9.4 ppm is shifted to -10 ppm and the resonance at 6.4 ppm is not observed. In the spectrum of methemoglobin at pH greater than or equal to 7.6 with or without inositol hexaphosphate, the resonance at -5.8 ppm is present, but not those at -10 and -6.4 ppm, suggesting that methemoglobin at high pH has an oxy-like structure. Two resonances (at -8.2 and -7.3 ppm) which remain invariant in the two quaternary structures could come from exchangeable protons in the alpha1beta1 subunit interface and/or other exchangeable protons in the hemoglobin molecule which undergo no conformational changes during the oxygenation process. These exchangeable proton resonances serve as excellent spectroscopic probes of the quaternary structures of the subunit interfaces in studies of the molecular mechanism of cooperative ligand binding to hemoglobin.
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PMID:A proton nuclear magnetic resonance study of the quaternary structure of human homoglobins in water. 113 70

A new haemoglobin variant with a decreased oxygen affinity is described, in which the substitution, alpha 94 (G1) Asp replaced by Asn, affects the alpha1beta2 contact alpha1G1-beta2G4. The relevance of this variant to our understanding of the importance of the hydrogen bond between alpha1G1 and beta2G4 in Perutz's model of oxyhaemoglobin A is discussed.
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PMID:Haemoglobin Titusville: alpha94 Asp replaced by Asn. A new haemoglobin with a lowered affinity for oxygen. 116 12


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