Multiple role of hydrophobicity of tryptophan-108 in chicken lysozyme: structural stability, saccharide binding ability, and abnormal pKa of glutamic acid-35

Yamada, Hidenori; Yasukochi, Takanori; Kuroki, Ryota; Miki, Takeyoshi; Horiuchi, Tadao; Imoto, Taiji

doi:10.1021/bi00139a017

Cited by 99 publications

(112 citation statements)

References 33 publications

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“…In hen egg white lysozyme, an abnormal pK a value of 6.3 was experimentally obtained for Glu 35 , which acts as the proton donor (6,7), and this is regarded as an important factor in this enzyme ability to retain its activity over a wide pH range. As described above, the corresponding proton donor carboxylate, Glu 22 , has a normal theoretical pK a value of 3.4 in chitosanase.…”

Section: Resultsmentioning

confidence: 99%

“…The carboxylate acting as the proton donor is usually in a specific environment, favorable to efficient proton donation; for example in hen egg white lysozyme, Glu 35 , which acts as the proton donor, is in a hydrophobic environment because of the van der Waals' contacts with the indole group of Trp 108 (6). This hydrophobic environment results in Glu 35 possessing a pK a value (6.3) higher than normal and creates a widely extended bell shape profile in the pH activity relationship (7). Clearly, the interaction of the proton donor carboxylate with other amino acid residues is a very important structural factor in determining the maximum activity of glycosyl hydrolases.…”

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confidence: 99%

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Theoretical Calculation of pKReveals an Important Role of Arg205 in the Activity and Stability of Streptomyces sp. N174 Chitosanase

Fukamizo¹,

Juffer²,

Vogel³

et al. 2000

Journal of Biological Chemistry

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Based on the crystal structure of chitosanase from Streptomyces sp. N174, we have calculated theoretical pK a values of the ionizable groups of this protein using a combination of the boundary element method and continuum electrostatics. The pK a value obtained for Arg 205 , which is located in the catalytic cleft, was abnormally high (>20.0), indicating that the guanidyl group may interact strongly with nearby charges. Chitosanases possessing mutations in this position (R205A, R205H, and R205Y), produced by Streptomyces lividans expression system, were found to have less than 0.3% of the activity of the wild type enzyme and to possess thermal stabilities 4 -5 kcal/mol lower than that of the wild type protein.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Theoretical Calculation of pKReveals an Important Role of Arg205 in the Activity and Stability of Streptomyces sp. N174 Chitosanase

Fukamizo¹,

Juffer²,

Vogel³

et al. 2000

Journal of Biological Chemistry

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“…For example, there are three tryptophan residues in the substrate-binding cleft of hen egg-white lysozyme, Trp62, Trp63, and Trp108. [22][23][24][25][26] Trp62 is expose to the solvent at subsite À3, but Trp63 is located relatively inside at the same subsite. Trp108 is located at subsite À2 but very close to the carboxyl side chain of Glu35.…”

Section: Discussionmentioning

confidence: 99%

Role of Tryptophan Residues in a Class V Chitinase fromNicotiana tabacum

Umemoto¹,

Ohnuma²,

Urpilainen³

et al. 2012

Bioscience, Biotechnology, and Biochemistry

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“…9,[50][51][52] Hydrophobic-induced acid-dissociation constant (pK a ) shifts of catalytic residues are important for enzyme activities. 57,58) In fact, the catalytic residues, Asp-25 and Asp-25Ј of the 1556 Vol. 31, No.…”

Section: Resultsmentioning

confidence: 99%

Determination of Ligand-Binding Sites on Proteins Using Long-Range Hydrophobic Potential

Yamaotsu

Oda

Hirono

2008

Biological & Pharmaceutical Bulletin

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Identifying the ligand-binding site in the three-dimensional (3D) structure of a target protein is a starting point for the rational design of therapeutic agents. Many procedures have been developed for the detection of binding sites in protein 3D structures. These are divided into two types of algorithms: those based on geometrical cavity detection in a protein, and those based on the detection of interaction points on a protein. The first type includes a surface method (MS), 2,3) grid-surface methods (Cavity Search 4) and VOIDOO, 5) ) alpha-shape methods derived from the Voronoi diagram (CAST 6) and VOLBL 7) ), a layer method using a probe (PASS), 8) and a mapping method using the hydrophobic groups on a protein surface. 9) These procedures are often unable to detect binding sites close to the protein surface or to identify more open binding sites. The second type includes the detection of interaction points by a probe using grid searching methods , DOCK [14][15][16] , QSiteFinder 17) and SiteMap 18) ) and a random searching method (MCSS). [19][20][21][22] These procedures used several probes (methane, water, etc.) to detect pockets on a protein, and then evaluated likelihoods of the binding site with detected pockets by physical or empirical functions (van der Waals, electrostatic, hydrogen-bonding, etc.). However, because the functions of these interactions are short range, the representation of a binding site on a protein is discrete and does not correspond to the whole binding site.Hydrophobicity is a key parameter for understanding drug activity 23,24) ; however, it has rarely been used in the identification of binding sites, because it is difficult to define. Hydrophobicity is usually measured and reported as a log P value, where P is the partition coefficient of the molecules in octanol/water. However, the dependency of the hydrophobic interaction on distance has remained unknown, and it has therefore been approximated by various functions of distance. Hydrophobic-potential functions that use lipophilic constants based on log P are known as molecular lipophilicity potentials (MLPs). [25][26][27][28][29][30][31][32][33] Audry's first MLP was based on a hyperbolic distance function, Eq. 1. 25,26)Here Kellogg et al. proposed HINT (Hydrophobic INTeractions) function which is atom-based, Eq. 3. 29-32)MLPϭs i a i s j a j exp(Ϫd ij )Here, hydrophobic atom constants, a i and a j , are multiplied by the solvent-accessible surface area of each atom, s i and s j . Gaillard et al. introduced the decay length of 2 Å into an exponential function, Eq. 4. 33)MLPϭf i f j exp(Ϫd ij /2)All of MLPs were fitted to the log P values of compounds on the assumption that they were situated in contact positions or associated positions. Therefore, the short decay length was calculated as 1 or 2 Å (Eqs. 2-4). Israelachvili and Pashley measured the hydrophobic interaction between two monolayer-coated mica surfaces in aqueous solutions, and approximated the results using the exponential expression shown in Eqs. 5a-c. 34)Here,...

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Multiple role of hydrophobicity of tryptophan-108 in chicken lysozyme: structural stability, saccharide binding ability, and abnormal pKa of glutamic acid-35

Cited by 99 publications

References 33 publications

Theoretical Calculation of pKReveals an Important Role of Arg205 in the Activity and Stability of Streptomyces sp. N174 Chitosanase

Theoretical Calculation of pKReveals an Important Role of Arg205 in the Activity and Stability of Streptomyces sp. N174 Chitosanase

Role of Tryptophan Residues in a Class V Chitinase fromNicotiana tabacum

Determination of Ligand-Binding Sites on Proteins Using Long-Range Hydrophobic Potential

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