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Response to Paoli

Nature Structural Biology volume 8, page 745 (2001)Cite this article

Paoli's analysis of archaeal and eukaryotic translation initiation factor 6 (aIF6 and eIF6, PDB codes 1G61, 1G62)1 and a pair of functionally distinct enzymes, L-arginine:glycine amidinotransferase (PDB code 1JDW)2 and L-arginine:inosamine-phosphate amidinotransferase (PDB code 1BWD)3, underscores the difficulties inherent in trying to establish a conceptual framework for protein fold classification. To paraphrase Holm and Sander4: Are the IF6s amidinotransferase α/β-propellers or are they like the amidinotransferase α/β-propellers? Attempts to answer this question will be further complicated by the fact that the IF6s correspond to only a portion of the amidinotransferases (184/360 residues). Moreover, the relative spatial locations of N- and C-termini within the IF6s are not the same in the amidinotransferases.

In the Groft et al.1 paper, we utilized a pragmatic definition of protein structure similarity based on a widely used automated structure-structure comparison tool (DALI5). At the time of publication of our original paper1, searching DALI with full-length proteins and each one of the five individual subdomains of either IF6 failed to detect either 1JDW or 1BWD. However, recent modifications to the DALI server now allow the relationship between eIF6 (or aIF6) and 1JDW to be identified (no relationship is returned for 1BWD because the DALI server considers 1JDW to be representative of both structures). Comparative protein structure modeling, which relies on primary sequence similarity, also failed to detect the fact that 1G61, 1G62, 1JDW, and 1BWD are similar. Subsequent pair-wise comparisons revealed the following root-mean-square-deviations: 1G62 versus 1JDW = 3.5 Å (184/360 α carbons, 8% identity) and 1G62 versus 1BWD = 3.5 Å (181/348 α carbons, 8% identity). For reference, 1G62 versus 1G61 = 1.5 Å (221/225 α carbons, 33% identity).

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Authors and Affiliations

  1. Rockefeller University, Molecular Biophysics and the Howard Hughes Medical Institute, 1230 York Avenue, New York, 10021-6399, NewYork, USA

    Caroline M. Groft, Roland Beckmann, Andrej Sali & Stephen K. Burley

Authors
  1. Caroline M. Groft
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  2. Roland Beckmann
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  3. Andrej Sali
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  4. Stephen K. Burley
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Correspondence to Stephen K. Burley.

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Groft, C., Beckmann, R., Sali, A. et al. Response to Paoli. Nat Struct Mol Biol 8, 745 (2001). https://doi.org/10.1038/nsb0901-745

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