Comment on Wang's paper on the covalent Cys‐X‐Lys bridges

Ruszkowski, M.; Dauter, Zbigniew

doi:10.1002/pro.3576

Cited by 6 publications

(5 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, it was not possible to determine the identity of the bridging atom; crystallographically, both were equally possible ( Figure 7 A–C). This illustrates the difficulty in determining the precise nature of the bridging atom, and there appears to be a divided debate on this topic [ 35 ].…”

Section: Resultsmentioning

confidence: 99%

Structural Features of Clostridium botulinum Neurotoxin Subtype A2 Cell Binding Domain

Gregory

Mahadeva

Liu

et al. 2022

Toxins

View full text Add to dashboard Cite

Botulinum neurotoxins (BoNT) are a group of clostridial toxins that cause the potentially fatal neuroparalytic disease botulism. Although highly toxic, BoNTs are utilized as therapeutics to treat a range of neuromuscular conditions. Several serotypes (BoNT/A-/G, /X) have been identified with vastly differing toxicological profiles. Each serotype can be further sub-categorised into subtypes due to subtle variations in their protein sequence. These minor changes have been attributed to differences in both the duration of action and potency for BoNT/A subtypes. BoNTs are composed of three domains—a cell-binding domain, a translocation domain, and a catalytic domain. In this paper, we present the crystal structures of the botulinum neurotoxin A2 cell binding domain, both alone and in complex with its receptor ganglioside GD1a at 1.63 and 2.10 Å, respectively. The analysis of these structures reveals a potential redox-dependent Lys-O-Cys bridge close to the ganglioside binding site and a hinge motion between the HCN and HCC subdomains. Furthermore, we make a detailed comparison with the previously reported HC/A2:SV2C structure for a comprehensive structural analysis of HC/A2 receptor binding.

show abstract

Section: Resultsmentioning

confidence: 99%

Structural Features of Clostridium botulinum Neurotoxin Subtype A2 Cell Binding Domain

Gregory

Mahadeva

Liu

et al. 2022

Toxins

View full text Add to dashboard Cite

show abstract

“…It is therefore surprising to observe a cross‐linker formed by these pair of residues. Still, the formation of single NOS bridges has now been confirmed after a long‐standing discussion [5, 25–28] . These observations have expanded, with further oxidation of the amino moiety of the Lys being confirmed.…”

Section: Introductionmentioning

confidence: 80%

“…Still, the formation of single NOS bridges has now been confirmed after a long-standing discussion. [5,[25][26][27][28] These observations have expanded, with further oxidation of the amino moiety of the Lys being confirmed. A double NOS bond involving two Cys and a Lys (SONOS) has been reported by different research groups in M pro .…”

Section: Introductionmentioning

confidence: 87%

Mechanisms of Cysteine‐Lysine Covalent Linkage—The Role of Reactive Oxygen Species and Competition with Disulfide Bonds**

Bazzi

Fritz

et al. 2023

Angew Chem Int Ed

View full text Add to dashboard Cite

Recently, a new naturally occurring covalent linkage was characterised, involving a cysteine and a lysine, bridged through an oxygen atom. The latter was dubbed as the NOS bond, reflecting the individual atoms involved in this uncommon bond which finds little parallel in lab chemistry. It is found to form under oxidising conditions and is reversible upon addition of reducing agents. Further studies have identified the bond in crystal structures across a variety of systems and organisms, potentially playing an important role in regulation, cellular defense and replication. Not only that, double NOS bonds have been identified and even found to be competitive in relation to the formation of disulfide bonds. This raises several questions about how this exotic bond comes to be, what are the intermediates involved in its formation and how it competes with other pathways of sulfide oxidation. With this objective in mind, we revisited our first proposed mechanism for the reaction with model electronic structure calculations, adding information about the reactivity with alternative reactive oxygen species and other potential competing products of oxidation. We present a network with more than 30 reactions which provides one of the most encompassing pictures for cysteine oxidation pathways to date.

show abstract

“…At first, the formation of single NOS bridges was reported. 4,[17][18][19][20] However, it has recently been shown that further oxidation of the amino moiety of the Lys is possible in the main protease of SARS-CoV-2 (M P ro ), leading to the formation of a double NOS bridge (SONOS). 5,21 It has also been observed that NOS bonds can be formed both in the presence of molecular oxygen and hydrogen peroxide in solution, the latter being somewhat faster.…”

Section: Introductionmentioning

confidence: 99%

A computational bird's eye view of redox reactivity in the formation of cysteine-lysine covalent linkages

Jin

Bazzi

Fritz

et al. 2022

Preprint

View full text Add to dashboard Cite

Recently, a new naturally occurring covalent linkage in peptides was characterised, involving a cysteine and a lysine, bridged through a single oxygen atom. The latter was dubbed as the NOS bond, reflecting the individual atoms directly involved in this rather uncommon bond which finds little parallel in lab chemistry. It is found to form under oxidising conditions and reversible upon addition of reducing agents. Further studies have shown that this bond is found over a large variety of systems and organisms, potentially playing an important role in regulation, cellular defense and replication. Not only that, double NOS bonds have been identified and even found to be competitive in relation to the formation of disulfide bonds. This raises several questions about how this exotic bond comes to be, what are the intermediates involved in its formation and how it competes with other pathways of sulfide oxidation (e.g., sulfinic acid formation, disulfide linkage). With this objective in mind, we revisited our first proposed mechanism for the reaction with model electronic structure calculations, adding information about the reactivity with alternative reactive oxygen species (ROS) and other potential competing products of oxidation. We present a reaction network with more than 30 intermediates which provides one of the most encompassing pictures for cysteine oxidation pathways to date.

show abstract

Comment on Wang's paper on the covalent Cys‐X‐Lys bridges

Cited by 6 publications

References 4 publications

Structural Features of Clostridium botulinum Neurotoxin Subtype A2 Cell Binding Domain

Structural Features of Clostridium botulinum Neurotoxin Subtype A2 Cell Binding Domain

Mechanisms of Cysteine‐Lysine Covalent Linkage—The Role of Reactive Oxygen Species and Competition with Disulfide Bonds**

A computational bird's eye view of redox reactivity in the formation of cysteine-lysine covalent linkages

Contact Info

Product

Resources

About