Lysine-cysteine NOS bonds
From Proteopedia
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<StructureSection size='350' side='right' caption='' scene='88/883792/6zx4_nos/2'> | <StructureSection size='350' side='right' caption='' scene='88/883792/6zx4_nos/2'> | ||
| - | Lysine-cysteine "Nitrogen-Oxygen-Sulfur" (NOS) bonds (<scene name='88/883792/6zx4_nos/2'>restore initial scene</scene>) were first reported in 2021 in transaldolases<ref name="wensien2021">PMID: 33953398</ref>. The sidechains of a lysine and a cysteine, joined by an NOS bond, make a covalent linkage between polypeptide chains. For comparison, the [[disulfide bond]] is a far more common type of covalent linkage between polypeptide chains, and the [[isopeptide bond]] is another rare type. | + | Lysine-cysteine "Nitrogen-Oxygen-Sulfur" (NOS) bonds (<scene name='88/883792/6zx4_nos/2'>restore initial scene</scene>) were first reported in 2021 in transaldolases<ref name="wensien2021">PMID: 33953398</ref>. The sidechains of a lysine and a cysteine, joined by an NOS bond, make a covalent linkage between polypeptide chains. For comparison, the [[disulfide bond]] is a far more common type of [[Protein crosslinks|covalent linkage between polypeptide chains]], and the [[isopeptide bond]] is another rare type. |
<scene name='88/883792/6zx4_nos_whole_molecule/1'>The NOS bond is located</scene> near the N-terminus of the 352 amino acid ''Neisseria gonorrhoeae'' transaldolase chain [[6zx4]], between Lys8 and Cys38, near the surface. | <scene name='88/883792/6zx4_nos_whole_molecule/1'>The NOS bond is located</scene> near the N-terminus of the 352 amino acid ''Neisseria gonorrhoeae'' transaldolase chain [[6zx4]], between Lys8 and Cys38, near the surface. | ||
Revision as of 15:53, 2 November 2021
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Contents |
Methods
This is a summary of the observations supporting the NOS bond[1]. 6zx4 (oxidized form, NOS present, enzyme inactive) has a resolution of 0.96 Å, with a better than average Rfree of 0.136. Neisseria gonorrhoeae transaldolase has 3 cysteines (no disulfide bonds). It does not form disulfide-linked oligomers. Each Cys was individually mutated to Ser. Only the mutation Cys38Ser abolished redox control, producing a constitutively active enzyme.
Electron density for an unidentified atom appeared between the sidechain nitrogen of Lys8 and the sulfur of Cys38 for several crystals under nonreducing conditions, as well as in data from a low-dose non-synchrotron source, arguing against a radiation damage artifact. Competitive refinements indicated that the unidentified atom was oxygen, rather than carbon. Mass spectrometry analysis was consistent with this conclusion.
In crystals of reduced (active) enzyme, the Lys8-O-Cys38 bridge was absent. However, electron density near the Cys38 sulfur was consistent with molecular oxygen O2. Molecular oxygen was absent in this position in the oxidized (inactive) enzyme.
See Also
- Electron density maps shows density maps for the bona fide NOS bond in 6zx4, as well as a presumably overlooked NOS bond in a structure published in 2011, and a case of Lys close to Cys where the electron density rules out an NOS bond.
Other Protein Crosslinks
In addition to the thioester bonds discussed above, other covalent cross-links between polypeptide chains include:
- Disulfide bonds
- Isopeptide bonds
- Thioester protein crosslinks
- Thioether protein crosslinks
- Ester protein crosslinks
- Histidine-tyrosine protein crosslinks
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Wensien M, von Pappenheim FR, Funk LM, Kloskowski P, Curth U, Diederichsen U, Uranga J, Ye J, Fang P, Pan KT, Urlaub H, Mata RA, Sautner V, Tittmann K. A lysine-cysteine redox switch with an NOS bridge regulates enzyme function. Nature. 2021 May 5. pii: 10.1038/s41586-021-03513-3. doi:, 10.1038/s41586-021-03513-3. PMID:33953398 doi:http://dx.doi.org/10.1038/s41586-021-03513-3
