Biochemical and Biophysical Research Communications

Oct.7, 2005

Dear Dr. Hartley,

After a careful review of your manuscript, I am afraid that we are not able to accept it for publication in BBRC in its current form. As you know, this is a rapid communication journal and not all submissions, regardless of their merit, are suitable for this format. Our standards are increasingly high, and in fact, more than 60% of submissions do not meet our criteria.

Should you wish to submit this work again to the journal, we ask that you significantly revise it based on the referee's commentary (see below) and submit it to the same editor with a cover-letter describing your point-by-point response to the comments. Please note that it will be processed as a new submission.

I am sorry to convey this negative decision; I know it is a disappointment. However, I thank you for the opportunity to see your work.

 

Best wishes,

Chin Ha Chung
 Editor
 Biochemical and Biophysical Research Communications

 

<Referee's comments>

The manuscript by Hartley describes the reconstruction of hydrophobic cores of the functional barstars by introducing a random set of hydrophobic residues. This is a technically interesting manuscript, but a number of changes should be made. Overall, the manuscript is too concise and the results are not discussed in any detail, which is frustrating to readers. I think that the manuscript should be reconsidered after making proper revisions listed below.

The complex structure of barstar and barnase by Buckle et al (1994) showed that barstar inhibits barnase by sterically blocking the active site with a helix (h2) and adjacent loop segment. Therefore, I think some active mutants might have a different fold without disrupting the local conformation of protein-protein interaction surface. Is there any experimental evidence (e.g. CD-spectroscopy data) that all the mutants have a same folding?

I think it is possible to make more detailed discussion regarding the folding of the protein by carefully analyzing the data of Table 1. For example, is there any change in total volume of hydrophobic residues in the mutants compared to that of wild type? Is it possible to construct and analyze the 3D models of the mutants to get an idea why the specific sets of residues listed in Table 1 are allowed in the hydrophobic core for the activity? It might also be worth examining the difference in amino acid sequence between the active and inactive mutants.

The several important experimental procedures are not described in the manuscript although their citations are in the references. For example, it is unclear how the author did the random mutations in the 22 positions which are scattered in the primary sequence. It would be comprehensible to readers if the sequences of the primers used and detailed procedures are also described in the manuscript.


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