Proteins: Strucure, Function and Bioinformatics is an international journal that published short communications on protein structures. There already has been a structure from a thermophilic methanogen GTP cyclohydrolase (Morrison et al.; Biochemistry, 47: 230-242, 2008). The main point of difference between our structure and the published structure, which has a 60% identical amino acid sequence, by Morrison et al. is that ours has one of the products in the active site (GMP).  On the other hand, GTP cyclohydrolase is currently still in use for high throuhgput screening in enzyme assays and derivatives are still under consideration that are derived from in silico screening. Consequently, there are potential IP issues, which are further discussed below  and is in the attched PDF to this ROI submission.

Background and potential IP consideration for publication of the M. ruminantium GTP cyclohydrolase structure.

The recent submission titled â??The Crystal Structure of GTP and GMP-Bound GTP Cyclohydrolase III from Methanobrevibacter ruminantium M1â?? through the ROI system describes the structural characterisation of the enzyme that catalyses the first step in the biosynthesis of the methanogen cofactor F420. There is a published structure already that shares 60% sequence identity at the amino acid level from Methanocaldococcus jannaschii (Morrison et al. 2008, Biochemistry 2008, 47:230-42). The already published structure contains GTP and three metal ions in the active site. The two structures are very similar overall, especially in the active site. What makes our structures a different is that one has a product of the reaction in the active site, GMP and it is from a rumen methanogen. The GTP cyclohydrolase is part of a three enzyme screening system that is currently in use that also contains mru CA and RibD (SM9). Some partial inhibitors at 20 at µM have been identified when the first 5000 compound library was screened and the top 6 compounds have been ordered for testing in rumen in vitro assays. The GTP cyclohydrolase may potentially be used to screen additional libraries this year. We recommend at this point that the paper not be published, but the issue be revisited when the inhibitor screening involving GTP cyclohydrolase is complete. 
