The evolution and structure of snake venom phosphodiesterase (svPDE) highlight its importance in venom actions

Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Taiwan
Department of Biostatistics, University of Oslo, Norway
Graduate Institute of Biomedical Sciences, Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taiwan
Institute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung University, Taiwan
Department of Life Science, National Tsing Hua University, Taiwan
Institute of Molecular and Cellular Biology, National Tsing Hua University, Taiwan

Apr 17, 2023

https://doi.org/10.7554/eLife.83966

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Accepted for publication after peer review and revision.

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Version of Record published: April 21, 2023 (This version)
Accepted Manuscript published: April 17, 2023 (Go to version)
Accepted: April 5, 2023
Preprint posted: November 24, 2022 (Go to version)
Received: October 5, 2022

Decision letter
Author response

Decision letter

Christian R Landry

Senior and Reviewing Editor; Université Laval, Canada
Melisa Benard Valle

Reviewer; Instituto de Biotecnologia, UNAM, Mexico

Our editorial process produces two outputs: i) public reviews designed to be posted alongside the preprint for the benefit of readers; ii) feedback on the manuscript for the authors, including requests for revisions, shown below. We also include an acceptance summary that explains what the editors found interesting or important about the work.

Decision letter after peer review:

Thank you for submitting your article "The evolution and structure of snake venom phosphodiesterase (svPDE) highlight its importance in venom actions" for consideration by eLife. Your article has been reviewed by 3 peer reviewers, and the evaluation has been overseen by a Reviewing Editor and Christian Landry as the Senior Editor. The following individual involved in the review of your submission has agreed to reveal their identity: Melisa Benard Valle (Reviewer #2).

The reviewers have discussed their reviews with one another, and the Reviewing Editor has drafted this to help you prepare a revised submission.

Essential revisions:

1) There are some technical questions about the crystal structures and the role of ions that should be clarified in the text.

2) There is missing information regarding the samples.

https://doi.org/10.7554/eLife.83966.sa1

Author response

Essential revisions:

1) There are some technical questions about the crystal structures and the role of ions that should be clarified in the text.

Supplementary File 2A has been updated to include the B factor of AMP.

As also suggested by Reviewer 3, the structural overlay of AMP bound to svPDE, ENPP3 and ENPP1 highlights similarities and differences with other ENPP family members, as shown in Figure 3—figure supplement 2.

(Line 257~262, sentences added)

“Moreover, the structural overlay of AMP-complexed svPDE, ENPP3 and ENPP1 shows that the lysine claw composed of K255, K278 and K528 in ENPP1, which interacts with the terminal phosphate of ATP, appears differently in svPDE or ENPP3 (Figure 3—figure supplement 2). While svPDE contains two conserved lysines (K184 and K455), only K185 is located close to the substrate. This suggests that svPDE has an ENPP3-like substrate specificity, due to ENPP3 contains only one conserved lysine (K205) in the active region.”

Since two zinc ions at the active site are essential for the enzymatic activity, it suggests that metal chelators previously reported as preclinical antidotes for the snakebite management [1] presumably could also exert its therapeutic effect via the inhibition of the svPDE enzymatic activities, in responses to the comments by Reviewer 1.

(Line 390~394, sentences added)

“In principle, the current preclinical antidote and repurposed metal chelators for snakebite victims (Dennis et al., 2020) could also function via the inhibition of svPDE by chelating Zinc ions. In addition, some of the inhibitors for ENPP family enzymes show promise as potential therapeutics for snakebite management.”

2) There is missing information regarding the samples.

This information has been included in the Materials and methods (LINE 401) and a supplementary table (Supplementary File 1). We thank the reviewer for pointing this out and updated the main text so that readers can find the information more easily as follows: (LINE 114~115, sentences updated) “included the draft one of Naja atra sequenced from a muscle tissue (ongoing internal project, see Materials and methods).”

(Line 137~138, sentences updated) “with the corresponding genomes available in the NCBI Assembly database (see Supplementary File 1 for sample details).”

https://doi.org/10.7554/eLife.83966.sa2