Table 1.
Conserved residues in the CYP51 family. Location and possible role (T. brucei numbering)
| Residue | Remark on conservation (if not 100% identical) |
Predicted role | Location/details |
|---|---|---|---|
| A). Residues identical in eukaryotic CYP51s (Residues shown in bold are 100% identical in bacterial CYP51s as well) | |||
| P33 | structural/folding | Follows the N-terminal membrane anchor, proline rich region, essential for P450 expression (nucleus for initial folding?) |
|
| G43* | structural | Starts αA’ | |
| P52 | structural | αA/ separates αA from αA’ by providing a sharp turn between them |
|
| G66 | structural | αA - β1-2/ Separates helix A and β1-2 strand allowing a sharp turn |
|
| T78 | unclear (folding?) | β1-2/ forms van der Waals contacts with the proline rich region |
|
| G81 | Misaligned in Trypanosomatidae (left shifted) |
structural | β1-2 – αB/ Separates β1-2 and helix B |
| Y103 | heme support/ substrate binding |
αB’ signature/H-bond with the ring A propionate, forms the surface of the substrate binding cavity |
|
| P108 | Y122 in Cunninghamella elegans (seq. error?) |
structural/(functional?) | αB’ signature /Turn within the B’ helix |
| F110 | substrate binding | αB’ signature/ forms the surface of the substrate binding cavity (possibly interacts with the sterol C16/the arm area) |
|
| G111 | structural | αB’ signature/ brakes αB’ | |
| V114 | L122 in Aphanomyces euteiches | unclear | αB’- αB” loop |
| Q126 | H in Schizosaccharomyces pombe (seq.error?) |
substrate binding | αC/ forms the surface of the substrate binding cavity, (sterol arm) |
| E149 | unclear | αD/proximal surface | |
| T178 | unclear | αE/ proximal surface | |
| A179 | unclear | αE/ proximal surface | |
| L183 | unclear | αE/ proximal surface | |
| G185 | structural | αF’/ Forms turn separating helices E and F’ | |
| R247 | T255 in Penicillum italicum (seq. error?) |
unclear | αG |
| Y270 | unclear | HI loop | |
| G292 | proton delivery route | αI /I-helix signature | |
| Q293 | proton delivery route | αI /I-helix signature | |
| H294 | proton delivery route | αI /I-helix signature/ H-bond with E205 | |
| T/S295 | S in filamentous fungi | proton delivery route | αI /I-helix signature/ “conserved threonine”, forms the surface of the substrate binding cavity |
| S296 | T261 in Citrus reticulate | unclear | αI//I-helix signature |
| W302 | G267 in Citrus reticulate (seq. error?) |
unclear | αI |
| E348 | structural | αK/ ExxR salt bridge | |
| I350 | I/L | unclear | αK |
| R351 | C372 in Mycosphaerella graminicola (seq. error?) |
structural | αK/ ExxR salt bridge |
| R361 | heme support | β1-4 /H-bond with the ring A propionate | |
| R404 | P404 in rice | unclear | αK’ - ηK” loop (meander) |
| F415 | heme binding area | αK’ - ηK” loop | |
| G416 | heme binding area | αK’ - ηK” loop | |
| G418 | heme binding area | ηK” | |
| H420 | R394 in Citrus reticulate (seq. error?) |
heme binding area | ηK’/H-bond with the ring D propionate |
| C422 | S439 in cotton (seq. error) | heme binding area | ηK”–αL loop/ iron coordinating Cys (the fifth axial ligand) |
| G424 | structural | ηK”–αL loop/ starts helix L | |
| B). Examples of conserved phyla-specific residues with predicted function | |||
| F105 | L (animals, fungi), I (T. cruzi, Monosiga brevicollis) |
substrate binding | αB’ signature/ forms the surface of the substrate binding cavity (sterol C4 atom area) |
| Y116 | F (plants) | heme support/ substrate binding |
αB”/H-bond with the ring D propionate (the same role in plants might play a Y located 4 residues (one turn) to the C-terminus (Y124 in potato sequence)), forms the surface of the substrate binding cavity |
| R124 | Conserved in Trypanosomatidae and bacteria |
heme support | αC/H-bond with the ring D propionate; the same role in other phyla must be played by the residue located one turn to the C-terminus: R (plants), K (fungi, animals: K156 in human) |
| L127 | F (plants), K (fungi, animals) | substrate binding | αC/ forms the surface of the substrate binding cavity (sterol arm) |
| P210 | H in vertebrates | substrate recognition? | αF”/forms the surface of the access channel entrance |
| V213 | F (fungi), W (animals) | substrate recognition? | αF”/forms the surface of the access channel entrance |
| M284 | L (plants), M/I/L (Fungi), M (animals) |
substrate binding | αI/ forms the surface of the substrate binding cavity (sterol arm) |
| L356 | I/L (fungi), I (animals) | substrate binding | αK-β1-4 loop/forms the surface of the substrate binding cavity (sterol C29[α]) |
| M360 | L/M/F (fungi) | substrate binding | β1-4/forms the surface of the substrate binding cavity (sterol C3-OH) |
| M460 | M/L (fungi) | substrate binding | β4 hairpin/forms the surface of the substrate binding cavity (sterol C3-OH) |
| V461 | F/V (fungi), I (animals) | substrate binding | β4 hairpin/forms the surface of the substrate binding cavity (sterol C29[α]) |