Homology modeling of the three membrane proteins of the dhurrin metabolon: catalytic sites, membrane surface association and protein–protein interactions
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Homology modeling of the three membrane proteins of the dhurrin metabolon : catalytic sites, membrane surface association and protein–protein interactions. / Jensen, Kenneth; Osmani, Sarah Anne; Hamann, Thomas; Naur, Peter; Møller, Birger Lindberg.
In: Phytochemistry, Vol. 72, No. 17, 2011, p. 2113-2123.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Homology modeling of the three membrane proteins of the dhurrin metabolon
T2 - catalytic sites, membrane surface association and protein–protein interactions
AU - Jensen, Kenneth
AU - Osmani, Sarah Anne
AU - Hamann, Thomas
AU - Naur, Peter
AU - Møller, Birger Lindberg
PY - 2011
Y1 - 2011
N2 - Formation of metabolons (macromolecular enzyme complexes) facilitates the channelling of substrates in biosynthetic pathways. Metabolon formation is a dynamic process in which transient structures mediated by weak protein–protein interactions are formed. In Sorghum, the cyanogenic glucoside dhurrin is derived from l-tyrosine in a pathway involving the two cytochromes P450 (CYPs) CYP79A1 and CYP71E1, a glucosyltransferase (UGT85B1), and the redox partner NADPH-dependent cytochrome P450 reductase (CPR). Experimental evidence suggests that the enzymes of this pathway form a metabolon. Homology modeling of the three membrane bound proteins was carried out using the Sybyl software and available relevant crystal structures. Residues involved in tight positioning of the substrates and intermediates in the active sites of CYP79A1 and CYP71E1 were identified. In both CYPs, hydrophobic surface domains close to the N-terminal trans-membrane anchor and between the F' and G helices were identified as involved in membrane anchoring. The proximal surface of both CYPs showed positively charged patches complementary to a negatively charged bulge on CPR carrying the FMN domain. A patch of surface exposed, positively charged amino acid residues positioned on the opposite face of the membrane anchor was identified in CYP71E1 and might be involved in binding UGT85B1 via a hypervariable negatively charged loop in this protein.
AB - Formation of metabolons (macromolecular enzyme complexes) facilitates the channelling of substrates in biosynthetic pathways. Metabolon formation is a dynamic process in which transient structures mediated by weak protein–protein interactions are formed. In Sorghum, the cyanogenic glucoside dhurrin is derived from l-tyrosine in a pathway involving the two cytochromes P450 (CYPs) CYP79A1 and CYP71E1, a glucosyltransferase (UGT85B1), and the redox partner NADPH-dependent cytochrome P450 reductase (CPR). Experimental evidence suggests that the enzymes of this pathway form a metabolon. Homology modeling of the three membrane bound proteins was carried out using the Sybyl software and available relevant crystal structures. Residues involved in tight positioning of the substrates and intermediates in the active sites of CYP79A1 and CYP71E1 were identified. In both CYPs, hydrophobic surface domains close to the N-terminal trans-membrane anchor and between the F' and G helices were identified as involved in membrane anchoring. The proximal surface of both CYPs showed positively charged patches complementary to a negatively charged bulge on CPR carrying the FMN domain. A patch of surface exposed, positively charged amino acid residues positioned on the opposite face of the membrane anchor was identified in CYP71E1 and might be involved in binding UGT85B1 via a hypervariable negatively charged loop in this protein.
U2 - 10.1016/j.phytochem.2011.05.001
DO - 10.1016/j.phytochem.2011.05.001
M3 - Journal article
VL - 72
SP - 2113
EP - 2123
JO - Phytochemistry
JF - Phytochemistry
SN - 0031-9422
IS - 17
ER -
ID: 34508683