Journal ArticleDOI
Structural insights into a low‐spin myoglobin variant with bis‐histidine coordination from molecular modeling
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TLDR
A functional model of NOR is engineered by creating a two His and one Glu non‐heme iron center in sperm whale myoglobin that adopts a low‐spin state with bis‐His coordination in the absence of metal ions binding to the designed metal center.Abstract:
Rational design of functional enzymes is a powerful strategy to gain deep insights into more complex native enzymes, such as nitric oxide reductase (NOR). Recently, we engineered a functional model of NOR by creating a two His and one Glu (2-His-1-Glu) non-heme iron center in sperm whale myoglobin (swMb L29E, F43H, H64, called FeBMb(-His)). It was found that FeBMb(-His) adopts a low-spin state with bis-His coordination in the absence of metal ions binding to the designed metal center. However, no structural information was available for the variant in this special spin state. We herein performed molecular modeling of FeBMb(-His) and compared with the X-ray structure of its copper bound derivative, Cu(II)-CN−-FeBMb(-His), resolved recently at a high resolution (1.65 A) (PDB entry 3MN0). The simulated structure shows that mutation of Leu to Glu at position 29 in the hydrophobic heme pocket alters the folding behavior of Mb. The hydrogen bond between Glu29 and His64 further plays a role in stabilizing the bis-His (His64/His93) coordination structure. This study offers an excellent example of using molecular modeling to gain insights in rational design of both structural and functional proteins. Proteins 2011. © 2010 Wiley-Liss, Inc.read more
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Structure and function of heme proteins in non-native states: a mini-review.
Ying-Wu Lin,Jiangyun Wang +1 more
TL;DR: The structure and function relationship of heme proteins in non-native states is thus as important as that in native states for elucidating the precise roles of heMe proteins in biological systems.
Journal ArticleDOI
Structure and function of heme proteins regulated by diverse post-translational modifications.
TL;DR: The tremendous progress made in research methods and advances in research techniques will make it possible to rationally control the diverse PTMs of heme proteins, especially those associated with human diseases, toward the authors' desired goals for a better life.
Journal ArticleDOI
Functional tuning and expanding of myoglobin by rational protein design.
Ying-Wu Lin,Jiangyun Wang,Yi Lu +2 more
TL;DR: Myoglobin (Mb), a small heme protein created by nature with diverse functions, has been shown to be an ideal scaffold for rational protein design, and the progress reviewed herein includes fine-tuning its native functions of O2 binding and transport, peroxidase activity and nitrite reductase (NIR) activity, and rational expanding its functionalities.
Journal ArticleDOI
A novel tyrosine-heme C−O covalent linkage in F43Y myoglobin: a new post-translational modification of heme proteins.
TL;DR: A novel tyrosine–heme covalent CO bond in an artificially produced sperm whale myoglobin mutant, F43Y Mb, which formed spontaneously in vivo between the Tyr43 hydroxy group and the heme 4‐vinyl group is reported.
Journal ArticleDOI
Rational heme protein design: all roads lead to Rome.
TL;DR: Rational heme protein designs focus on the modification of the heme-binding active site and the he me group, protein hybridization and domain swapping, and de novo design, which provide unique advantages for illustrating the structure-property-reactivity-function (SPRF) relationship of heme proteins in nature.
References
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Accessible Surface Areas as a Measure of the Thermodynamic Parameters of Hydration of Peptides
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