A critical view on conservative mutations
By analysing the surface composition of a set of protein 3D structures, complemented with predicted surface compositional information for homologous proteins, we have found significant evidence for a layer composition of protein structures. In the innermost and outermost parts of proteins there is a...
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| Published in | Protein engineering Vol. 14; no. 6; pp. 397 - 402 |
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| Main Authors | , |
| Format | Journal Article |
| Language | English |
| Published |
England
Oxford Publishing Limited (England)
01.06.2001
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| Subjects | |
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| Abstract | By analysing the surface composition of a set of protein 3D structures, complemented with predicted surface compositional information for homologous proteins, we have found significant evidence for a layer composition of protein structures. In the innermost and outermost parts of proteins there is a net negative charge, while the middle has a net positive charge. In addition, our findings indicate that the concept of conservative mutation needs substantial revision, e.g. very different spatial preferences were found for glutamic acid and aspartic acid. The alanine screening often used in protein engineering projects involves the substitution of residues to alanine, based on the assumption that alanine is a "neutral" residue. However, alanine has a high negative correlation with all but the non-polar residues. We therefore propose the use of, for example, serine as a substitute for the residues that are negatively correlated with alanine. |
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| AbstractList | By analysing the surface composition of a set of protein 3D structures, complemented with predicted surface compositional information for homologous proteins, we have found significant evidence for a layer composition of protein structures. In the innermost and outermost parts of proteins there is a net negative charge, while the middle has a net positive charge. In addition, our findings indicate that the concept of conservative mutation needs substantial revision, e.g. very different spatial preferences were found for glutamic acid and aspartic acid. The alanine screening often used in protein engineering projects involves the substitution of residues to alanine, based on the assumption that alanine is a "neutral" residue. However, alanine has a high negative correlation with all but the non-polar residues. We therefore propose the use of, for example, serine as a substitute for the residues that are negatively correlated with alanine. |
| Author | Petersen, S B Jonson, P H |
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| Cites_doi | 10.1002/prot.340200303 10.1136/gut.46.5.707 10.1126/science.3892686 10.1002/(SICI)1097-0134(19990515)35:3<293::AID-PROT3>3.0.CO;2-L 10.1021/bi991422s 10.1002/pro.5560010313 10.1093/protein/3.8.659 10.1006/jmbi.1996.0114 10.1111/j.1399-3011.1986.tb01046.x 10.1093/nar/26.1.313 10.1093/protein/7.5.645 10.1021/bi00127a005 10.1006/jmbi.1997.1498 10.1093/protein/12.7.535 10.1093/genetics/149.1.445 10.1002/(SICI)1097-0134(19990815)36:3<347::AID-PROT9>3.0.CO;2-3 10.1093/protein/6.3.267 10.1016/S0168-1656(98)00153-9 10.1179/naw.1976.14.1.008 10.1016/S0022-2836(77)80200-3 10.1002/pro.5560030317 10.1002/pro.5560010203 10.1093/protein/12.1.31 10.1016/0022-2836(87)90038-6 10.1006/jmbi.1994.1330 10.1007/s002140050428 10.1093/protein/12.12.1025 10.1006/jmbi.1999.2826 10.1073/pnas.92.26.12136 10.1002/(SICI)1097-0134(199605)25:1<38::AID-PROT4>3.3.CO;2-H 10.1006/jmbi.1999.3091 10.1111/j.1399-3011.1987.tb02228.x 10.1146/annurev.bi.47.070178.001343 10.1093/nar/25.1.31 10.1021/bi961801a |
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| SubjectTerms | Amino Acid Sequence Aspartic Acid - chemistry Glutamic Acid - chemistry Ions Models, Molecular Mutation Protein Conformation Sequence Homology, Amino Acid Solvents - pharmacology Static Electricity |
| Title | A critical view on conservative mutations |
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