COMPACTNESS DETERMINES PROTEIN FOLDING TYPE

2008 ◽  
Vol 06 (04) ◽  
pp. 667-680 ◽  
Author(s):  
OXANA V. GALZITSKAYA ◽  
NATALYA S. BOGATYREVA ◽  
DMITRY N. IVANKOV
Keyword(s):  
Protein Folding ◽  
Amino Acid ◽  
Size Range ◽  
Accessible Surface Area ◽  
Amino Acid Residues ◽  
Homologous Proteins ◽  
Folding Rates ◽  
The Difference ◽  
Accessible Surface ◽  
Ideal Sphere

We have demonstrated here that protein compactness, which we define as the ratio of the accessible surface area of a protein to that of the ideal sphere of the same volume, is one of the factors determining the mechanism of protein folding. Proteins with multi-state kinetics, on average, are more compact (compactness is 1.49 ± 0.02 for proteins within the size range of 101–151 amino acid residues) than proteins with two-state kinetics (compactness is 1.59 ± 0.03 for proteins within the same size range of 101–151 amino acid residues). We have shown that compactness for homologous proteins can explain both the difference in folding rates and the difference in folding mechanisms.

Influence of Blood Group and Secretor Status on Carbohydrate Structures in Human Gastric Mucins: Implications for Peptic Ulcer

1995 ◽  
Vol 89 (4) ◽  
pp. 405-415 ◽  
Author(s):  
R. L. Sidebotham ◽  
J. H. Baron ◽  
J. Schrager ◽  
J. Spencer ◽  
J. R. Clamp ◽  
...  
Keyword(s):  
Peptic Ulcer ◽  
Amino Acid ◽  
Blood Group ◽  
Average Length ◽  
Amino Acid Residues ◽  
Secretor Status ◽  
Increased Risk ◽  
The Mean ◽  
The Difference ◽  
Carbohydrate Chains

1. The content and distribution of carbohydrate was examined in mucus glycopolypeptides from human antral mucosae. 2. The mean amount of carbohydrate per 1000 amino acid residues was found to be similar in glycopolypeptides with A, B or H activity. It was slightly, though significantly, less in glycopolypeptides lacking these determinants, because carbohydrate chains were of a shorter average length than in the A-, B- or H-active preparations. This difference was reflected in the sizes of oligosaccharide—alcohols released from representative glycopolypeptides with alkaline borohydride. 3. Differences between A-, B- or H-active and non-secretor glycopolypeptides in terms of the mean number of carbohydrate chains per 1000 amino acid residues were found to be small, and without significance. 4. The average number of peripheral monosaccharide units per 1000 amino acid residues was greater in A-active than in H-active, and least in non-secretor, glycopolypeptides. This order was reversed for monosaccharide units incorporated into skeletal (core plus backbone) structures. The difference in each case was statistically significant. 5. These findings suggest that the increased risk of peptic ulcer associated with blood group O and non-secretor status is unlikely to be attributable to an inherent deficiency in the protective mucus layer, linked to differences between mucins that are associated with A, B or H activity. Other hypotheses linked to infection with Helicobacter pylori are examined.

Studies on Chymotrypsin-P. I. Characterization

1971 ◽  
Vol 49 (9) ◽  
pp. 999-1004 ◽  
Author(s):  
M. C. Shaw ◽  
T. Viswanatha
Keyword(s):  
Molecular Weight ◽  
Amino Acid ◽  
Physicochemical Properties ◽  
Gel Filtration ◽  
Amino Acid Residues ◽  
The Difference ◽  
Filtration Technique

The physicochemical properties of chymotrypsin-P obtained by the papain activation of chymotrypsinogen have been investigated. The molecular weight of this enzyme as determined by gel filtration technique has been found to be 24 000 ± 1000. The amino acid residues occupying the N-terminal positions and the composition of the B- and C-chains of chymotrypsin-P are identical with those found in α-chymotrypsin. Thus the difference between the two enzymes is restricted to the composition of their A-chains.

Human Coagulation Factor Va Interaction with Phospholipid Vesicles: A Molecular Dynamics Study.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1699-1699
Author(s):  
Tivadar Orban ◽  
Michael Kalafatis
Keyword(s):  
Amino Acid ◽  
Lipid Bilayer ◽  
Factor Xa ◽  
Accessible Surface Area ◽  
Fatty Acyl ◽  
Phospholipid Bilayer ◽  
Solvent Accessible Surface Area ◽  
Factor Va ◽  
Accessible Surface ◽  
Simulation Time

Abstract The prothrombinase complex, the enzyme responsible for the timely conversion of prothrombin to thrombin, is composed of factor Xa (the enzyme), factor Va (the cofactor) assembled on the activated cell surface in the presence of divalent metal ions. In our quest to propose a model of the prothrombinase complex we first created a homology model in solution of factor Va (pdb code 1y61). Next we created a mixed phospholipid bilayer model composed of 1-palmitoyl, 2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) and 1-palmitoyl, 2-oleoyl-sn-glycero-3-phosphatidylserine (POPS) in a 4:1 ratio. The lipid bilayer was equilibrated for 10 ns. The data showed that the average area per head group and the deuterium order parameters of the fatty acyl chains compare well with the previously reported nuclear magnetic resonance data. We next created a system composed of factor Va, water molecules, phospholipid bilayer composed of POPS/POPC and sodium ions. Factor Va was placed at the near interface of the equilibrated POPC/POPS phospholipid bilayer but making sure that the two entities were not interacting. Molecular dynamics simulation was then performed on the entire system. Distance analysis performed between the center of masses of the factor Va molecule and the lipid bilayer revealed that during the 4.5 ns simulation time, the factor Va molecule gets inserted into the interface of the hydrophobic core of the bilayer. The distance between the two centers of masses decreased during the 4.5 ns simulation time from 92 Å to 78 Å. At the end of the 4.5 ns simulation time the indole moieties of Trp2063 and Trp2064 were found to be in the vicinity of the ester and the fatty acyl chain moieties of the phospholipids. Factor Va was found to participate in hydrogen bonds formation with both the carboxylate and the phosphate groups of POPS. Following 4.5 ns simulation time the farthest amino acid residue away from the membrane is located at ~ 100 Å from the lipid bilayer plane. This result is in agreement with previous fluorescence energy transfer studies that concluded that a domain of membrane-bound factor Va is positioned at a minimum distance of 90 Å above the membrane surface. It is noteworthy that the amino acid sequence comprising Pro1663 to Val1672 of factor Va had a root mean square displacemenent (RMSD) 4.5 times higher as the average RMSD of the other residues, i.e., 9 Å. This sequence is highly hydrophobic in nature and it was previously shown to contain a membrane binding site on factor Va. However, the present placement of factor Va on the lipid bilayer does not allow the insertion of this hydrophobic patch into the lipid bilayer. We next tested the hypothesis whether the region encompassing amino acid residues Glu323 to Val331 gets exposed to solvent following the interaction of factor Va with the phospholipids. This region was shown to contain a binding site of factor Xa on factor Va. Solvent accessible surface area calculated for each amino acid residue of the Glu323 to Val331 sequence revealed that during the 4.5 ns simulation time the solvent accessible surface area does not increase. In conclusion, our work proposes for the first time a model of factor Va bound to a mixed POPC/POPS lipid bilayer and provides the necessary framework that accounts for the presence of phospholipids as a major regulatory component of a protein complex. This model can be extrapolated to the study of the dynamics of other membrane associated complexes involved in blood coagulation.

The Influence of Dipeptide Composition on Protein Folding Rates

2011 ◽  
Vol 378-379 ◽  
pp. 157-160
Author(s):  
Jian Xiu Guo ◽  
Ni Ni Rao
Keyword(s):  
Protein Folding ◽  
Amino Acid ◽  
Amino Acid Sequences ◽  
Dipeptide Composition ◽  
Coupling Effects ◽  
Jackknife Test ◽  
Folding Rates ◽  
Important Challenge ◽  
The Relationship

Understanding the relationship between amino acid sequences and folding rates of proteins is an important challenge in computational and molecular biology. All existing algorithms for predicting protein folding rates have never taken into account the sequence coupling effects. In this work, a novel algorithm was developed for predicting the protein folding rates from amino acid sequences. The prediction was achieved on the basis of dipeptide composition, in which the sequence coupling effects are explicitly included through a series of conditional probability elements. Based on a non-redundant dataset of 99 proteins, the proposed method was found to provide an excellent agreement between the predicted and experimental folding rates of proteins when evaluated with the jackknife test. The correlation coefficient was 87.7% and the standard error was 2.04, which indicated the important contribution from sequence coupling effects to the determination of protein folding rates.

scholarly journals Determination of three amino acids causing alteration of proteolytic activities of staphylococcal glutamyl endopeptidases

2009 ◽  
Vol 390 (3) ◽  
Author(s):  
Takayuki K. Nemoto ◽  
Toshio Ono ◽  
Yu Shimoyama ◽  
Shigenobu Kimura ◽  
Yuko Ohara-Nemoto
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Protease Activity ◽  
Binding Pocket ◽  
Catalytic Triad ◽  
Amino Acid Residues ◽  
Proteolytic Activities ◽  
Hydrophobic Amino Acids ◽  
The Difference

Abstract Staphylococcus aureus, Staphylococcus epidermidis, and Staphylococcus warneri secrete glutamyl endopeptidases, designated GluV8, GluSE, and GluSW, respectively. The order of their protease activities is GluSE<GluSW<<GluV8. In the present study, we investigated the mechanism that causes these differences. Expression of chimeric proteins between GluV8 and GluSE revealed that the difference is primarily attributed to amino acid residues 170–195, which define the intrinsic protease activity, and additionally to residues 119–169, which affect the proteolytic sensitivity. Among nine substitutions present in residues 170–195 of the three proteases, the substitutions at positions 185, 188, and 189 were responsible for the changes in their activities, and the combination of W185, V188, and P189, which naturally occurs in GluV8, exerts the highest protease activity. W185 and P189 were indispensable for full activity, but V188 could be replaced by hydrophobic amino acids. These three amino acid residues appear to create a substrate-binding pocket together with the catalytic triad and the N-terminal V1, and therefore define the K m values of the proteases. We also describe a method to produce a chimeric form of GluSE and GluV8 that is resistant to proteolysis, and therefore possesses 4-fold higher activity than the wild-type recombinant GluV8.

scholarly journals Study on the Influence of mRNA, the Genetic Language, on Protein Folding Rates

2021 ◽  
Vol 12 ◽  
Author(s):  
Ruifang Li ◽  
Hong Li ◽  
Xue Feng ◽  
Ruifeng Zhao ◽  
Yongxia Cheng
Keyword(s):  
Protein Folding ◽  
Amino Acid ◽  
Protein Structures ◽  
Gc Content ◽  
Amino Acid Sequences ◽  
Information Redundancy ◽  
Folding Rate ◽  
Folding Rates ◽  
Related Information ◽  
Linear Regressions

Many works have reported that protein folding rates are influenced by the characteristics of amino acid sequences and protein structures. However, few reports on the problem of whether the corresponding mRNA sequences are related to the protein folding rates can be found. An mRNA sequence is regarded as a kind of genetic language, and its vocabulary and phraseology must provide influential information regarding the protein folding rate. In the present work, linear regressions on the parameters of the vocabulary and phraseology of mRNA sequences and the corresponding protein folding rates were analyzed. The results indicated that D2 (the adjacent base-related information redundancy) values and the GC content values of the corresponding mRNA sequences exhibit significant negative relations with the protein folding rates, but D1 (the single base information redundancy) values exhibit significant positive relations with the protein folding rates. In addition, the results show that the relationships between the parameters of the genetic language and the corresponding protein folding rates are obviously different for different protein groups. Some useful parameters that are related to protein folding rates were found. The results indicate that when predicting protein folding rates, the information from protein structures and their amino acid sequences is insufficient, and some information for regulating the protein folding rates must be derived from the mRNA sequences.

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