Fig. 8

DissectHMMER analysis of HEM1_METKA. The domain hits can mainly be generalized as cellular metabolism reactions and can be further subdivided into 2 main groups : (i) 10 anabolic reactions that combine simple substances into more complex molecules driven by NADP+ and (ii) 2 catabolic reactions that breaks complex organic molecules into simpler substances driven by NAD+. With the exception of the IlvN domain (PF07991.7), the top 9 domain hits Shikimate_DH (PF01488.15), F420_oxidored (PF03807.12), THF_DHG_CYH_C (PF02882.14), NAD_binding_2 (PF03446.10), 2-Hacid_dh_C(PF02826.14), adh_short (PF00106.20), KR (PF08659.5), NAD_binding_7 (PF13241.1) and NAD_binding_10 (PF13460.1) are NADP+ driven anabolic processes with a total FPR range of between 0.0 and 0.06 and a structural-derived %Id range of between 9.0 and 14. In the case of the IlvN domain, its sequence-to-domain hit covers only 42 % (75 out of 177 AA) of its NADP+ domain and found by HMMER3 alone. As a result, the total FPR is regretfully high at 1.07 as the HMMER algorithm reaches its limit of detection. The next group of domain hits i.e. GFO_IDH_MocA (PF01408.17) and Malic_M (PF03949.10) binds the NAD+ molecule. This group exhibits a larger total FPR range of between 0.20 and 0.70 and a lower structural-derived %Id of between 6.4 and 9.4. Notably, there was a noticeable jump between the adjacent hits from 0.06 (NAD_binding_10) to 0.20 (GFO_IDH_MocA) when the ligand changes from NADP+ to NAD+ between the anabolic and catabolic groups