Native or promiscuous? Analyzing putative dimethylsulfoniopropionate lyases using a substrate proofing approach

@article{Lei2017NativeOP,
  title={Native or promiscuous? Analyzing putative dimethylsulfoniopropionate lyases using a substrate proofing approach},
  author={Lei Lei and K. Cherukuri and Diana Meltzer and Uria Alcolombri and Dan S. Tawfik},
  journal={bioRxiv},
  year={2017}
}
Enzyme promiscuity is widely spread. Foremost, within superfamilies, the native function of one enzyme is typically observed as promiscuous activity in related enzymes. The native function usually exhibits high catalytic efficiency while promiscuous activities are weak, but this is not always the case. Thus, for certain enzymes it remains questionable whether their currently known activity is native or promiscuous. Dimethylsulfon-iopropionate (DMSP) is an abundant marine metabolite cleaved via… 
View via Publisher
biorxiv.org

References

SHOWING 1-10 OF 44 REFERENCES
Enzyme Promiscuity and Evolution of New Protein Functions
This chapter introduces the various categories of promiscuity and their possible role in enzyme evolution. It also reviews some of the well-known examples of enzymes for which the promiscuous…
Shared promiscuous activities and evolutionary features in various members of the amidohydrolase superfamily.
TLDR
A diverse and partially overlapping pattern of promiscuous activities are found in these enzymes, including a significant lactonase activity in PTE, esterase activities in both PTE and PHP, and a weak PTE activity in DHO.
The dddP gene of Roseovarius nubinhibens encodes a novel lyase that cleaves dimethylsulfoniopropionate into acrylate plus dimethyl sulfide.
TLDR
DddP represents a second, wholly different class of DMSP lyase that cleaves DMSP to DMS plus acrylate from DMSP, and resembles those members of the M24B family, such as creatinase, which also act on a non-peptide substrate and have no metal cofactor.
A quantitative index of substrate promiscuity.
TLDR
A quantitative index of promiscuity (I) that can be calculated from the catalytic efficiencies of an enzyme toward a defined set of substrates is defined and a weighted promiscuit index (J) that accounts for patterns of similarity and dissimilarity among the substrates in the set is defined.
Structural and Biochemical Insights into Dimethylsulfoniopropionate Cleavage by Cofactor-Bound DddK from the Prolific Marine Bacterium Pelagibacter.
TLDR
Crystal structures of cofactor-bound DddK reveal key metal ion binding and catalytic residues and provide the first rationalization for varying activities with different metal ions.
Biochemical, Kinetic, and Spectroscopic Characterization of Ruegeria pomeroyi DddW—A Mononuclear Iron-Dependent DMSP Lyase
TLDR
The studies show that as-purified DddW is a metalloenzyme, like the DddQ and DddP DMSP lyases, but contains an iron cofactor, andMeasurements of metal binding affinity and catalytic activity indicate that Fe(II) is most likely the preferred catalytic metal ion with a nanomolar binding affinity.
DddY, a periplasmic dimethylsulfoniopropionate lyase found in taxonomically diverse species of Proteobacteria
TLDR
An enzyme, DddY, is described, which cleaves DMSP into DMS plus acrylate and is located in the bacterial periplasm, unlike other DMSP lyases that catalyse this reaction.
DddQ, a novel, cupin-containing, dimethylsulfoniopropionate lyase in marine roseobacters and in uncultured marine bacteria.
TLDR
Ruegeria pomeroyi DSS-3, a marine roseobacter, can catabolize dimethylsulfoniopropionate, a compatible solute that is made in large amounts by marine plankton and algae, and has two different genes, dddP and dddQ, which encode enzymes that cleave DMSP, generating DMS plus acrylate.
New Mechanistic Insight from Substrate- and Product-Bound Structures of the Metal-Dependent Dimethylsulfoniopropionate Lyase DddQ.
TLDR
The structure of the DMSP-Fe(III)-DddQ structure reveals conformational changes associated with substrate binding and shows that DMSP is positioned optimally to bind iron and is in the proximity of Tyr 120 that acts as a Lewis base to initiate catalysis.
Distinct Metal Isoforms Underlie Promiscuous Activity Profiles of Metalloenzymes.
TLDR
This study systematically investigates how metals alter the activity profiles of five functionally diverged enzymes of the metallo-β-lactamase (MBL) superfamily and suggests that promiscuous activities of metalloenzymes can stem from an ensemble of metal isoforms in the cell, which could facilitate the functional divergence of met allopathic enzymes.
...
1
2
3
4
5
...