Extended Data Fig. 4: Loops in PYROXD1 allosterically control its activity.

(a) Sequence conservation analysis of loop 1 in PYROXD1. Figure was generated using WebLogo38. Black line indicates a conserved sequence motif (motif 1) in loop 1. (b) Detailed view of the projected paths of loop 1 and loop 2 in PYROXD1 (light blue) within the PYROXD1-RTCB complex, overlaid with cryo-EM map density (light grey). (c) Structural superposition of PYROXD1 bound to FAD (orange, PDB: 6ZK7)19 and PYROXD1 in complex with RTCB (pink). Clashes are indicated by a dotted circle. (d) Sequence conservation analysis of loop 2 in PYROXD1. Black line indicates a conserved sequence motif (motif 2) in loop 2. (e) Vector map displaying the structural rearrangements in the NAD(P)H binding ___domain upon NAD(P)H binding and complex formation with RTCB. (f) Zoom-in views of the FAD binding site free PYROXD1 (orange, PDB: 6ZK7)19 and PYROXD1 in complex with RTCB and NADH (light blue). (g) Conformation of the ordered part of Loop 2 in the PYROXD1-RTCB complex, overlaid with cryo-EM map density (light grey).