Structural and mechanistic comparisons of the metal-binding members of the vicinal oxygen chelate (VOC) superfamily

He, Panqing; Moran, Graham R.

doi:10.1016/j.jinorgbio.2011.06.006

Cited by 69 publications

(88 citation statements)

References 119 publications

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“…FosB is a member of the vicinal oxygen chelate (VOC) superfamily. VOCs are metalloenzymes that catalyze a diverse set of reactions, but all coordinate a divalent metal cation through vicinal oxygen atoms of a substrate, intermediate or transition state in the reaction [55]. FosB was identified before the discovery of bacillithiol, and cysteine was believed to be the thiol cofactor of FosB [45].…”

Section: Identification Of Bacillithiol-dependent and Bacillithiol-relamentioning

confidence: 99%

Bacillithiol: a key protective thiol inStaphylococcusaureus

Perera¹,

Newton²,

Pogliano³

2015

Expert Review of Anti-infective Therapy

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Bacillithiol is a low-molecular-weight thiol analogous to glutathione and is found in several Firmicutes, including Staphylococcus aureus. Since its discovery in 2009, bacillithiol has been a topic of interest because it has been found to contribute to resistance during oxidative stress and detoxification of electrophiles, such as the antibiotic fosfomycin, in S. aureus. The rapid increase in resistance of methicillin-resistant Staphylococcus aureus (MRSA) to available therapeutic agents is a great health concern, and many research efforts are focused on identifying new drugs and targets to combat this organism. This review describes the discovery of bacillithiol, studies that have elucidated the physiological roles of this molecule in S. aureus and other Bacilli, and the contribution of bacillithiol to S. aureus fitness during pathogenesis. Additionally, the bacillithiol biosynthesis pathway is evaluated as a novel drug target that can be utilized in combination with existing therapies to treat S. aureus infections.

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Section: Identification Of Bacillithiol-dependent and Bacillithiol-relamentioning

confidence: 99%

Bacillithiol: a key protective thiol inStaphylococcusaureus

Perera¹,

Newton²,

Pogliano³

2015

Expert Review of Anti-infective Therapy

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“…All of these enzymes share a common βαβββ fold module that provides the environment for metal coordination promoting direct electrophilic participation of the metal ion in catalysis (with the notable exception of the non-enzymatic bleomycin- and mitomycin-binding proteins (32)). This common module is combined and permuted in at least six distinct ways in the different enzymes in the superfamily (33), each associated with different types of reactions, including nucleophilic opening of epoxide, oxidative cleavage of a C–C bond, isomerization, and epimerization.…”

Section: Many Types Of Structural Variation Accompany Evolution Of Nementioning

confidence: 99%

New Insights about Enzyme Evolution from Large Scale Studies of Sequence and Structure Relationships

Brown

Babbitt

2014

Journal of Biological Chemistry

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Understanding how enzymes have evolved offers clues about their structure-function relationships and mechanisms. Here, we describe evolution of functionally diverse enzyme superfamilies, each representing a large set of sequences that evolved from a common ancestor and that retain conserved features of their structures and active sites. Using several examples, we describe the different structural strategies nature has used to evolve new reaction and substrate specificities in each unique superfamily. The results provide insight about enzyme evolution that is not easily obtained from studies of one or only a few enzymes.

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“…A similar number of interactions in the metal-binding vicinal oxygen chelate proteins were described in a recent review. 17 …”

Section: The Cupin Fold and The Consensus Mechanismmentioning

confidence: 99%

Imposing function down a (cupin)-barrel: secondary structure and metal stereochemistry in the αKG-dependent oxygenases

2013

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The Fe(II)/αketoglutarate (αKG) dependent oxygenases catalyze a diverse range of reactions significant in biological processes such as antibiotic biosynthesis, lipid metabolism, oxygen sensing, and DNA and RNA repair. Although functionally diverse, the eight-stranded β-barrel (cupin) and HX(D/E)XnH facial triad motifs are conserved in this super-family of enzymes. Crystal structure analysis of 25 αKG oxygenases reveals two stereoisomers of the Fe cofactor, Anti and Clock, which differ in the relative position of the exchangeable ligand position and the primary substrate. Herein, we discuss the relationship between the chemical mechanism and the secondary coordination sphere of the αKG oxygenases, within the constraints of the stereochemistry of the Fe cofactor. Sequence analysis of the cupin barrel indicates that a small subset of positions constitute the second coordination sphere, which has significant ramifications for the structure of the ferryl intermediate. The competence of both Anti and Clock stereoisomers of Fe points to a ferryl intermediate that is 5 coordinate. The small number of conserved close contacts within the active sites of αKG oxygenases can be extended to chemically related enzymes, such as the αKG-dependent halogenases SyrB2 and CytC3, and the non-αKG dependent dioxygenases isopenicillin N synthase (IPNS) and cysteine dioxygenase (CDO).

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Structural and mechanistic comparisons of the metal-binding members of the vicinal oxygen chelate (VOC) superfamily

Cited by 69 publications

References 119 publications

Bacillithiol: a key protective thiol inStaphylococcusaureus

Bacillithiol: a key protective thiol inStaphylococcusaureus

New Insights about Enzyme Evolution from Large Scale Studies of Sequence and Structure Relationships

Imposing function down a (cupin)-barrel: secondary structure and metal stereochemistry in the αKG-dependent oxygenases

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