Lysozyme among the Lilliputians

Rose, George D.

doi:10.1073/pnas.97.2.526

Cited by 4 publications

(3 citation statements)

References 26 publications

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“…Indeed, an astronomical number of sequences are generated by the combination of the 20 natural amino acids at each site of a sequence, but few of these can fold into native, fully functional protein structures. However, the information contained in natural amino acid sequences is redundant (2,3); namely, a small fraction of the information can fully determine a protein structure (4,5). Protein sequence simplification has emerged as a method of choice in deciphering the determinants of protein structures.…”

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confidence: 99%

Crystal structure of an extensively simplified variant of bovine pancreatic trypsin inhibitor in which over one-third of the residues are alanines

Islam¹,

Sohya²,

Noguchi

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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We report the high-resolution crystal structures of an extensively simplified variant of bovine pancreatic trypsin inhibitor containing 20 alanines (BPTI-20st) and a reference single-disulfide-bonded variant (BPTI-[5,55]st) at, respectively, 1.39 and 1.09 Å resolutions. The sequence was simplified based on the results of an alanine scanning experiment, as reported previously. The effects of the multiple alanine substitutions on the overall backbone structure were surprisingly small (C ␣ atom RMSD of 0.53 Å) being limited to small local structural perturbations. Both BPTI variants retained a wild-type level of trypsin inhibitory activity. The side-chain configurations of residues buried in the hydrophobic cores (<30% accessible surface area) were almost perfectly retained in both BPTI-20st and BPTI-[5,55]st, indicating that neither multiple alanine replacements nor the removal of the disulfide bonds affected their precise placements. However, the side chains of three partially buried residues (Q31, R20, and to some extent Y21) and several unburied residues rearranged into alternative dense-packing structures, suggesting some plasticity in their shape complementarity. These results indicate that a protein sequence simplified over its entire length can retain its densely packed, native side-chain structure, and suggest that both the design and fold recognition of natively folded proteins may be easier than previously thought.native structure ͉ protein design ͉ protein folding ͉ protein structure ͉ sequence simplification T he protein folding problem (1), or how a protein structure is encoded in its amino acid sequence, remains fundamentally unsolved. Indeed, an astronomical number of sequences are generated by the combination of the 20 natural amino acids at each site of a sequence, but few of these can fold into native, fully functional protein structures. However, the information contained in natural amino acid sequences is redundant (2, 3); namely, a small fraction of the information can fully determine a protein structure (4, 5). Protein sequence simplification has emerged as a method of choice in deciphering the determinants of protein structures.Information redundancy can be conceptually classified into class and site redundancy (6). Class redundancy refers to the overlapping physicochemical properties of the amino acids, and it can be removed by designing proteins with a reduced amino acid alphabet (7). Class redundancy has been reported in the Src SH3 domain, for which a functional variant with 70% of its sequence encoded by only five amino acids types was identified by phage display (8). Similarly, simplified variants of chorismate mutase (9) and orotate phosphoribosyl transferase (10), with sequences predominantly encoded by only nine amino acid types, rescued auxotrophic host cells lacking the respective enzymes.Site redundancy refers to the occurrence of several residues in a protein's amino acid sequence that do not contribute to the formation of the structure, except that their backbone atoms act as l...

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confidence: 99%

Crystal structure of an extensively simplified variant of bovine pancreatic trypsin inhibitor in which over one-third of the residues are alanines

Islam¹,

Sohya²,

Noguchi

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…In this formula, K is defined as a volume of serum (mL) that caused 50% hemolysis, and the dilution factor for this test was 0.01. The activity of lysozyme in the serum was determined using the method described by Rose (2000). Accordingly, 50 μL of each sample were mixed in sodium phosphate buffer (40 mM, pH 6.5) and transferred to a 96-well plate.…”

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confidence: 99%

Dietary Incorporation of Bacillus subtilis and Bacillus licheniformis Mixture (DiPro Aqua) Ameliorates Growth Performance, Immune Response, and Intestinal Morphology in Rainbow Trout

2021

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The current study was designed to investigate the role of a commercial probiotic containing equal proportions (1:1) of Bacillus subtilis and B. licheniformis spores (1.6 × 10 12 CFU/kg; DiPro Aqua) on the growth, immune response, and intestinal morphology of Rainbow Trout Oncorhynchus mykiss. A total of 168 Rainbow Trout fry were randomly divided into four groups and were fed diets with different doses of DiPro Aqua (control: 0 CFU/kg; treatment 1 [T1]: 8 × 10 8 CFU/kg; T2: 16 × 10 8 CFU/kg; T3: 24 × 10 8 CFU/kg) for 56 d. The highest body weight gain and specific growth rate were obtained in the T2 and T3 groups. In addition, the highest feed conversion ratio was measured in the control group. The results showed that the serum total immunoglobulins and total protein content were increased in fish that were fed the T2 and T3 diets compared to those that received the T1 and control diets (P < 0.05). The highest alternative complement pathway hemolytic activity was measured in T2 fish compared to the other groups. According to the antibacterial activity of the skin mucus samples against Yersinia ruckeri, dietary levels of DiPro Aqua improved the mucus bactericidal activity and the maximum effect was recorded in the T2 group. The dietary levels of the probiotic mixture, especially in T2, increased the villus length, villus width, and crypt depth within the distal intestine compared to those in the control group. In conclusion, the optimal dietary dose of DiPro Aqua to boost growth performance, immunity, and intestinal morphology in Rainbow Trout was 2.0 × 10 8 CFU/kg based on polynomial regression analysis.In today's world, aquaculture plays the most crucial role in providing seafood for humans due to the growing population and the depletion of wild fishery stocks. Intensive and super-intensive aquaculture operations are developed to produce more fish and shellfish, while the most important issues faced in these production systems are poor water quality, infectious disease outbreak, and exposure to various stressors that can negatively affect the growth performance and survival rate of cultured aquatic animals (Banerjee and Ray 2017;Rico et al. 2017). In this context, fish farmers commonly use a wide range of antibiotics and chemotherapeutics for controlling and treating infectious diseases (Dawood et al. 2018;Abdel-Latif et al. 2020). In some cases, antibiotics are no longer effective in treating pathogens due to antibiotic-resistant germs (Han et al. 2015;Dawood et al. 2020). Among several alternative strategies, the use of natural feed additives such as probiotics, prebiotics, and symbiotics to improve the growth performance and immune system of fish has recently increased to make the aquaculture industry profitable and sustainable (

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“…1 However, experimental studies have shown that much of the information is redundant, 2,3 and that a small fraction of it is sufficient for fully specifying a native protein structure. 4 Information redundancy is demonstrated experimentally by investigating the structure and the function of simplified proteins, with some or all excess information removed from their sequences. 5 The excess information in an amino acid sequence can be conceptually classified into two types: site redundancy and class redundancy.…”

Section: Introductionmentioning

confidence: 99%

Thermodynamic Properties of BPTI Variants with Highly Simplified Amino Acid Sequences

Kato

Yamada

Nakamura

et al. 2007

Journal of Molecular Biology

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Lysozyme among the Lilliputians

Cited by 4 publications

References 26 publications

Crystal structure of an extensively simplified variant of bovine pancreatic trypsin inhibitor in which over one-third of the residues are alanines

Crystal structure of an extensively simplified variant of bovine pancreatic trypsin inhibitor in which over one-third of the residues are alanines

Dietary Incorporation of Bacillus subtilis and Bacillus licheniformis Mixture (DiPro Aqua) Ameliorates Growth Performance, Immune Response, and Intestinal Morphology in Rainbow Trout

Thermodynamic Properties of BPTI Variants with Highly Simplified Amino Acid Sequences

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