Lysine-cysteine NOS bonds: Difference between revisions
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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'> | ||
Covalent Lysine-Cysteine protein crosslinks were first reported in 2016, interpreted at the time as Lys-CH<sub>2</sub>-Cys<ref name="methylene">PMID: 27261771</ref><ref name="matthews">PMID: 34180568</ref>. In 2019, Jimin Wang provided evidence for oxygen rather than methylene as the linker<ref name="jimin">PMID: 30592103</ref><ref name="dauterletter">PMID: 30666728</ref>. In 2021, Wensien ''et al.'' with the Tittmann group (Goettingen), studying [[Transaldolase]], put the Lysine-cysteine "Nitrogen-Oxygen-Sulfur" (NOS) protein crosslink on firm ground (<scene name='88/883792/6zx4_nos/2'>restore initial scene</scene>)<ref name="wensien2021">PMID: 33953398</ref><ref name="nandv">PMID: 33953388</ref><ref name="matthews" />. The sidechains of a lysine and a cysteine, joined by an NOS bond, make a covalent linkage between amino acids in a polypeptide chain (or 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. | |||
Covalent Lysine-Cysteine protein crosslinks were first reported in 2016, interpreted at the time as Lys-CH<sub>2</sub>-Cys<ref name="methylene">PMID: 27261771</ref><ref name="matthews">PMID: 34180568</ref>. In 2019, Jimin Wang provided evidence for oxygen rather than methylene as the linker<ref name="jimin">PMID: 30592103</ref><ref name="dauterletter">PMID: 30666728</ref>. In 2021, Wensien ''et al.'' with the Tittmann group (Goettingen), studying | |||
<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. | ||
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*Oxidized: NOS bond present, enzyme inactive. | *Oxidized: NOS bond present, enzyme inactive. | ||
</StructureSection> | |||
__NOTOC__ | |||
==Prevalence== | ==Prevalence== | ||
A survey of the data in the [[Protein Data Bank]] revealed that the NOS bond likely exists "in diverse protein families across all domains of life (including ''Homo sapiens'') and that it is often located at catalytic or regulatory hotspots."<ref name="wensien2021" /> Because the NOS bond was unknown before | A survey of the data in the [[Protein Data Bank]] revealed that the NOS bond likely exists "in diverse protein families across all domains of life (including ''Homo sapiens'') and that it is often located at catalytic or regulatory hotspots."<ref name="wensien2021" /> They found that about 100-150 or ~0.3% of entries in the PDB with resolutions of 2.0 Å or better have Lys-Cys NOS bonds<ref name="prevalence">PMID: 35165445</ref>. Because the NOS bond was unknown before 2019, it was often overlooked in earlier interpretations of [[electron density maps]].<ref name="wensien2021" /> Three examples are given illustrating putative NOS bonds in active sites of enzymes which, if correct, were previously overlooked: | ||
*[[1m3q]], a DNA glycosylase: Lys249 – Cys253. | *[[1m3q]] 2004, a DNA glycosylase: Lys249 – Cys253. | ||
*[[5y72]], a prenyltransferase: Lys275 – Cys223. | *[[5y72]] 2018, a prenyltransferase: Lys275 – Cys223. | ||
*[[6t3x]], a cytomegalovirus nuclear egress protein: Lys132 – Cys54. | *[[6t3x]] 2020, a cytomegalovirus nuclear egress protein: Lys132 – Cys54. | ||
==Methods== | ==Methods== | ||
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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 O<sub>2</sub>. Molecular oxygen was absent in this position in the oxidized (inactive) enzyme. | 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 O<sub>2</sub>. Molecular oxygen was absent in this position in the oxidized (inactive) enzyme. | ||
==Detection and Visualization== | |||
[[FirstGlance in Jmol]] automatically detects Lys-Cys NOS bonds and alerts you to their presence. For example, [http://firstglance.jmol.org/fg.htm?mol=6zx4 take a look at 6zx4 in FirstGlance]. It lists crosslinks and with one click on each, zooms in to show you the crosslink in atomic detail. Viewing the electron density map for the crosslink is just one more click. See the practical guide [[FirstGlance/Evaluating Protein Crosslinks]]. FirstGlance also alerts you [http://firstglance.jmol.org/versions.htm#crosslinks a number of other kinds of protein crosslinks]. | |||
==See Also== | ==See Also== | ||
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==Other Protein Crosslinks== | ==Other Protein Crosslinks== | ||
In addition to the | In addition to the bonds discussed above, other [[Protein crosslinks|covalent cross-links between polypeptide chains]] include: | ||
*[[Disulfide bond]]s | *[[Disulfide bond]]s | ||
*[[Isopeptide bond]]s | *[[Isopeptide bond]]s | ||