2NWD
Structure of chemically synthesized human lysozyme at 1 Angstrom resolution
Summary for 2NWD
| Entry DOI | 10.2210/pdb2nwd/pdb |
| Descriptor | Lysozyme C (2 entities in total) |
| Functional Keywords | native chemical ligation, chemical protein synthesis, convergent synthesis, hydrolase |
| Cellular location | Secreted: P61626 |
| Total number of polymer chains | 1 |
| Total formula weight | 14720.69 |
| Authors | Durek, T.,Torbeev, V.Y.,Kent, S.B.H. (deposition date: 2006-11-14, release date: 2006-12-19, Last modification date: 2024-10-30) |
| Primary citation | Durek, T.,Torbeev, V.Y.,Kent, S.B. Convergent chemical synthesis and high-resolution x-ray structure of human lysozyme. Proc.Natl.Acad.Sci.Usa, 104:4846-4851, 2007 Cited by PubMed Abstract: In this article, we report the total chemical synthesis of human lysozyme. Lysozyme serves as a widespread model system in various fields of biochemical research, including protein folding, enzyme catalysis, and amyloidogenesis. The 130-aa wild-type polypeptide chain of the human enzyme was assembled from four polypeptide segments by using native chemical ligation in a fully convergent fashion. Key to the assembly strategy is the application of the recently developed kinetically controlled ligation methodology, which provides efficient control over the ligation of two peptide (alpha)thioesters to yield a unique product. This result enables the facile preparation of a 64-residue peptide (alpha)thioester; this segment is joined by native chemical ligation to a 66-aa Cys peptide, to yield the target 130-aa polypeptide chain. The synthetic polypeptide chain was folded in vitro into a defined tertiary structure with concomitant formation of four disulfides, as shown by 2D TOCSY NMR spectroscopy. The structure of the synthetic human lysozyme was confirmed by high-resolution x-ray diffraction, giving the highest-resolution structure (1.04 A) observed to date for this enzyme. Synthetic lysozyme was obtained in good yield and excellent purity and had full enzymatic activity. This facile and efficient convergent synthesis scheme will enable preparation of unique chemical analogs of the lysozyme molecule and will prove useful in numerous areas of lysozyme research in the future. PubMed: 17360367DOI: 10.1073/pnas.0610630104 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.04 Å) |
Structure validation
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