Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The temperature and pH functions of the myeloma IgG(K) conformation were studied by optical rotatory dispersion, circular dichroism, thermal perturbation difference spectroscopy, solvent perturbation difference spectroscopy, electrochemical iodination and difference adiabatic scanning microcalorimetry. 2. The IgG studied was found to be capable of a fully reversible structural change between pH 6.5 and 6.0. A transition occurring at low pH is accompanied by an increase of exposure of the chromophores to the solvent. 3. The "alkaline state" was found to be capable of a fully reversible S-like transition at temperatures between 25 and 35 degrees C. The changes occurring at the higher temperature are accompanied by the screening of 14-15 tyrosine residues and probably by a small increase in the helicity of the protein. These changes are not accompanied by an appreciable heat effect. The thermal denaturation of the "alkaline state" occurs only at 64 degrees C in the narrow temperature interval (3-4 degrees C). 4. The "acid state" is not accompanied by S-like transition at 25-35 degrees C. The thermal denaturation of the "acid state" occurs at 54 degrees C in the wide temperature interval (8-9 degrees C). 5. It was proposed that the ionisation of the invariant histidine residues situated in the "cavity" between the constant and variable domains causes the pH transition studied. The temperature changes in the interval 25-35 degrees C are explained by the alteration of the domains interposition. Similar alterations were investigated as a result of antigen-antibody reaction.
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PMID:Temperature and pH dependent changes of immunoglobulin G structure. 23 15

In order to test the concepts that aminoacyl-tRNAs in plasmacytomas may on the one hand modulate the protein synthesized or on the other hand reflect the structure of the synthesized protein, the RPC-5 chromatographic profiles of aminoacyl-tRNAs for all 20 amino acids were studied in tRNA prepared from normal mouse liver and 11 plasmacytomas. The patterns of isoaccepting tRNA were compared with the structure of the myeloma protein being synthesized. The elution profiles of aminoacyl-tRNAs for nine of the amino acids were constant, i.e. they were the same for liver and all plasmacytomas. Significant variability was observed in the profiles of the other 11 families of aminoacyl-tRNAs: asparagine, serine and tryptophan, had peaks of isoaccepting tRNAs found in tumors and not in liver; glutamic acid, histidine and lysine, had different patterns of aminoacyl-tRNAs in plasmacytomas which could be distinguished from the elution profile of liver; and isoleucine, proline, threonine and tyrosine, showed pattern variability in only a few of the tumors. Valyl-tRNA uniquely had one isoacceptor present in liver but absent in the tumors. This variability is thought to be associated with different posttranscriptional modification of the tRNAs rather than regulation of individual tRNA genes in response to particular amino acid sequences in secreted myeloma proteins. Similarily, the lack of correlation of isoacceptors with sequence differences makes the modulation of protein fine structure by tRNA availability unlikely.
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PMID:Transfer ribonucleic acids from eleven immunoglobulin-secreting mouse plasmacytomas. Constant and variable chromatographic profiles compared with the myeloma protein sequences. 25 44

1. The temperature function of the myeloma IgG(K) IVA, Bence-Jones protein (K-type) IVA and its fragments (Fab(t), Fc'(t), VL and CL) was studied by thermal perturbation difference spectroscopy and circular dichroism. 2. The IgG and Bence-Jones protein studied were found to be capable of a fully reversible structural changes at temperatures between 25 and 35 degrees C. The changes occurring at the higher temperature are accompanied by the screening of the significant part of exposed tyrosine residues. The transition is not accompanied by an appreciable change in the main IgG secondary structure-beta-pleated sheet, according to the CD data. 3. It was found that the temperature-dependent changes of IgG occur in its Fab fragments, the changes of Bence-Jones protein occur in its variable part (VL domains). 4. The temperature changes in the interval 25-35 degrees C are explained by the flexibility of amino acid side chains composed hypervariable loops delineated the "sides" of cavity between variable domains.
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PMID:Temperature-dependent changes of myeloma immunoglobulin G (K) IVA, Bence-Jones protein (K-type) IVA and its fragments. 40 51

Amino acid sequence analysis of the pFc' fragment obtained by pepsin digestion of an IgG3; G3m(g) human myeloma protein HER shows it to consist of 112 residues. It starts at position 334 (gamma1 numbering), contains eight residues of the Cgamma2 region, and the whole Cgamma3 domain. Comparison with the sequence of gamma1 shows five differences including an extra Met at 397. Each is accountable by a single base substitution. The sequence is identical to that of a G3m(b0) molecule except for the previously noted allotype related Tyr/Phe exchange at position 436. The high degree of homology (95%) among gamma-chain subclasses suggests a recent diversification.
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PMID:The amino acid sequence of a human immunoglobulin G3m(g) pFc' fragment. 40

Six hundred and twelve mouse plasmacytomas were screened for hapten binding by using eleven different bacteriophage-hapten conjugates (phage T4 conjugated with haptens NP, NIP, DIP, DNP,BOC-ABA-Tyr, ABA-NP, ABA-MIP, ABS-HOP, PAB-HOP, penicillin G, cloxacillin). Fifteen ascites fluids (2.4%) inactivated at least one of the phage conjugates at a high dilution indicating binding. The specificity of these reactions was studied by titrating one ascites fluid with phage conjugates carring unrelated haptens, and by inhibiting the phage inactivation with free haptens. Of the 15 myeloma proteins, 10 had high titers (at least 30 times higher than the ascites fluid background) with the NIP-cap phage or the NP-cap phage or both. Four had high titers with the DNP-cap phage and one with the ABA-MIP phage. Thirteen of the 15 myeloma proteins were IgA, one was IgM and one IgG2b.
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PMID:A search for hapten-binding mouse plasmacytoma proteins. 43 27

Studies on a single component human cryoimmunoglobulin (cryo-IgG) (gamma 1 : lambda, Gm 4) were undertaken to gain a better understanding of the conformational stability of macromolecular interfaces essential for self-association of cryo-IgG leading to the formation of visible gel mass. Changes in the gross and localized conformation of cryo-IgG and a monoclonal IgG (gamma 1 : lambda, Gm 4) isolated from a myeloma patient (Hy) (Hy IgG) (gamma 1 : lambda, Gm 4) in alkaline media were determined by analytical ultracentrifugation, fluorescence characteristics, tyrosine ionization and H+ titration. Ultracentrifugal studies revealed that major transition in gross conformation took place at pH 11.4 for cryo-IgG and pH 11.7 for Hy IgG, whereby the number of charges and tyrosine residues exposed to aqueous environment was 110 and 26 for cryo-IgG, and 111 and 48 for Hy IgG, respectively. Beyond this transition pH fragmentation of both the proteins occurred and cryo-IgG lost its capacity for gel formation. Self-association of cryo-IgG was observed upto pH 11.4 in decreasing order with increase in denaturation pH. Cryo-IgG renatured from exposure to higher alkaline pH upto pH 11.4, showed the capability for forming gel, in spite of the irreversible local conformational changes as established by direct and reverse fluorimetric titration and tyrosine ionization studies. Cryo-IgG could be maintained in the optically clear sol phase at pH 10.5, at which pH 12 out of 62 tyrosine residues became exposed to aqueous media. There are distinct differences in the accessibility of tyrosine residues of cryo-IgG and Hy IgG as reflected in their tyrosine ionization profiles.
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PMID:Conformational stability of a human cryoglobulin. 54 39

The conformational changes of antibody structure induced by hapten molecule binding were investigated by means of thermal perturbation difference spectroscopy. The studies of the free rabit anti-dinitrophenyl antibodies show the conformational transition at temperatures between 25 and 35 degrees C. The changes occurring at the higher temperature are accompanied by the screening of the significant part of exposed tyrosine residues. Binding of the hapten molecules induces a similar transition to that which occurs between the two temperature dependent states of the free antibody. In contrast to our previous results with anti-dansyl rabbit antibodies the dinitrophenyl lysine stabilizes the "low temperature" native state of the protein. The investigation of the MOPC-315 mouse immunoglobulin A myeloma protein possessing anti-dinitrophenyl activity indicates no conformational transition at temperatures between 25 and 35 degrees C and only a small decrease of tyrosine exposure induced by the hapten binding. Our present and previous results indicate that most of the free immunoglobulins exist in two native conformational states which have a small difference in free energy. Hapten binding causes the transition in equilibrium between the two states towards the one of better binding. It is possible that this transition is necessary but not sufficient step for inducing the effector function of antibodies.
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PMID:Conformational transitions of antibodies induced by hapten binding. 56 Aug 70

The binding of Tnp (2,4,6-trinitrophenyl) derivatives to the Fv fragment (variable region of heavy and light chains) of the mouse myeloma IgA protein MOPC 315 was investigated by 270MHz proton nuclear magnetic resonance. Two of the haptens, Tnp-glycine and Tnp-l-aspartate, are in fast exchange with the Fv fragment, and the changes in chemical shifts for both protein and hapten resonances were determined by titrations. For the tightly binding hapten epsilon-N-Tnp-alpha-N-acetyl-l-lysine, which is in slow exchange with the Fv fragment, the changes in chemical shifts for the hapten H(3)+H(5) resonances were determined by cross-saturation. By using these data and the known structure of the combining site of protein MOPC 315 [Dwek, Wain-Hobson, Dower, Gettins, Sutton, Perkins & Givol (1977), Nature (London) 266, 31-37] the mode of binding of Tnp derivatives is deduced by ring-current calculations. The trinitrophenyl ring stacks with tryptophan-93(L) (light chain) in the ;aromatic box' formed by tryptophan-93(L), tyrosine-34(L) and phenyl-alanine-34(H) (heavy chain). Further evidence for the stacking interaction with a tryptophan residue is provided by the similarity of the optical-difference spectra observed with Tnp-aminomethylphosphonate in the presence of either the Fab fragment (light chain and N-terminal half of heavy chain) of protein MOPC 315 or tryptophan. These data show that the modes of binding of all the Tnp derivatives are very similar, despite a 100-fold range in their affinities. It is also concluded that the modes of binding of Dnp (2,4-dinitrophenyl) and Tnp derivatives to protein MOPC 315 are very similar, and that the structural basis for this is that the aromatic box is large enought to allow the trinitrophenyl ring to stack with tryptophan-93(L) while still forming hydrogen bonds to asparagine-36(L) and tyrosine-34(L).
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PMID:The binding of 2,4,6-trinitrophenyl derivatives to the mouse myeloma immunoglobulin A protein MOPC 315. 62 44

An effect of salt concentration on the human myeloma immunoglobulin G structure was studied by means of circular dichroism, thermal perturbation difference spectroscopy and isoelectric focusing in a pH gradient created by a concentration gradient of glucose in borate buffer solution. Immunoglobulin G (K) Iva showed a significant shift of isoelectric point to the alkaline region as a result of the increase in salt concentration. The difference spectra indicated a change in the exposure of tyrosine residues as a result of increase in salt concentration. No changes in the circular dichroic spectra with salt concentration were observed between 205 and 250 nm. Spectral changes observed for the undigested immunoglobulin G molecule are more marked than those observed for the isolated Fab fragments.
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PMID:Effect of salt concentration on immunoglobulin G structure. 64 22

The relation between structure and specificity of antibodies has been explored by 19F NMR studies of the binding of trifluoromethyl analogues of nitrophenyl haptens to the three mouse myeloma immunoglobulins M315, M460, and X25. We have used haptens with trifluoromethyl groups located at the ortho or para positions of the phenyl ring or attached to the side chain, two atoms removed from the ring (i.e.,-NHCH2CF3). The changes in chemical shift between hapten free in solution and bound to antibody are sensitive to microenvironment and range from 1.7-ppm downfield to 1-ppm upfield. The shifts of p-trifluoromethylnitrophenyl haptens bound to M315 and M460 are both large downfield shifts, which are likely caused by van der Waals interaction and ring-current effects, particularly from tyrosine-34(L); these haptens do not show similar shifts when bound to X25 which has a deletion of tyrosine34(L). Other differences in the binding of the aromatic rings of haptens by M315, M460, and X25 are observed and their origins considered. The importance of hydrogen bonding in the thermodynamic affinity of antibody for hapten has been estimated by comparisons of binding affinities for haptens with trifluoromethyl groups in place of nitro groups.
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PMID:Relation between structure and specificity of antibodies: nuclear magnetic resonance study of binding fluorine-19 labeled nitrophenyl haptens to myeloma immunoglobulins M315, M460, and X25. 69 4


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