TY - JOUR
T1 - Comparing the electronic properties and docking calculations of heme derivatives on CYP2B4
AU - Mendieta-Wejebe, Jessica E.
AU - Rosales-Hernández, Martha C.
AU - Rios, Hulme
AU - Trujillo-Ferrara, José
AU - López-Pérez, Gilberto
AU - Tamay-Cach, Feliciano
AU - Ramos-Morales, Rafael
AU - Correa-Basurto, José
N1 - Funding Information:
The authors thank CONACYT (62488) and SIP-COFAA/IPN (20070140) for their financial support.
PY - 2008/6
Y1 - 2008/6
N2 - Cytochrome P-450 is a group of enzymes involved in the biotransformation of many substances, including drugs. These enzymes possess a heme group (1) that when it is properly modified induces several important physicochemical changes that affect their enzymatic activity. In this work, the five structurally modified heme derivatives 2-6 and the native heme 1 were docked on CYP2B4, (an isoform of P450), in order to determine whether such modifications alter their binding form and binding affinity for CYP2B4 apoprotein. In addition, docking calculations were used to evaluate the affinity of CYP2B4 apoprotein-heme complexes for aniline (A) a nd N-methyl-aniline (NMA). Results showing the CYP2B4 heme 4- and heme 6-apoprotein complex es to be most energetically stable indicate that either hindrance effects or electronic properties are the most important factors with respect to the binding of heme derivatives at the heme-binding site. Furthermore, although all heme-apoprotein complexes demonstrated high affinity for both A and NMA, the CYP2B4 apoprotein-5 complex had higher affinity for A, and the heme 6 complex had higher affinity for NMA. Finally, surface electronic properties (SEP) were calculated in order to explain why certain arginine residues of CYP2B4 apoprotein interact with polarizable functionalities, such as ester groups or sp2 carbons, present in some hem e derivates. The main physicochemical parameter involved in the recognition process of the heme derivatives, the CYP2B4 apoprotein and A or NMA, are reported.
AB - Cytochrome P-450 is a group of enzymes involved in the biotransformation of many substances, including drugs. These enzymes possess a heme group (1) that when it is properly modified induces several important physicochemical changes that affect their enzymatic activity. In this work, the five structurally modified heme derivatives 2-6 and the native heme 1 were docked on CYP2B4, (an isoform of P450), in order to determine whether such modifications alter their binding form and binding affinity for CYP2B4 apoprotein. In addition, docking calculations were used to evaluate the affinity of CYP2B4 apoprotein-heme complexes for aniline (A) a nd N-methyl-aniline (NMA). Results showing the CYP2B4 heme 4- and heme 6-apoprotein complex es to be most energetically stable indicate that either hindrance effects or electronic properties are the most important factors with respect to the binding of heme derivatives at the heme-binding site. Furthermore, although all heme-apoprotein complexes demonstrated high affinity for both A and NMA, the CYP2B4 apoprotein-5 complex had higher affinity for A, and the heme 6 complex had higher affinity for NMA. Finally, surface electronic properties (SEP) were calculated in order to explain why certain arginine residues of CYP2B4 apoprotein interact with polarizable functionalities, such as ester groups or sp2 carbons, present in some hem e derivates. The main physicochemical parameter involved in the recognition process of the heme derivatives, the CYP2B4 apoprotein and A or NMA, are reported.
KW - Cytochrome P450
KW - DFT
KW - Docking
KW - HOMO-LUMO orbitals
KW - Heme derivatives
UR - http://www.scopus.com/inward/record.url?scp=43849112513&partnerID=8YFLogxK
U2 - 10.1007/s00894-008-0294-z
DO - 10.1007/s00894-008-0294-z
M3 - Artículo
C2 - 18478283
SN - 1610-2940
VL - 14
SP - 537
EP - 545
JO - Journal of Molecular Modeling
JF - Journal of Molecular Modeling
IS - 6
ER -