Prediction of interaction mode between a typical ACE inhibitor and MMP-9 active site.
To characterize the inhibitory specificity of angiotensin converting enzyme (ACE) inhibitors for matrix metalloproteinase 9 (MMP-9) activity, molecular modeling of these complex was performed referring the recent X-ray structure analyses using lisinopril as an ACE inhibitor. Two interaction modes differing in the orientation of the inhibitor on the active site were identified. Lisinopril was effectively stabilized by specific hydrogen bonds and hydrophobic interactions in the active site of MMP-9, and its hydrophobic group appeared to interact preferentially with the S1 site compared with the S1' site. These findings showed that ACE inhibitors could become important seeds for cardiovascular protection and the development of MMP inhibitors.
Yamamoto
Daisuke
D
Biomedical Computation Center, Osaka Medical College, 2-7 Daigakuchou, Takatsuki, Osaka, Japan. center@art.osaka-med.ac.jp
Takai
Shinji
S
Miyazaki
Mizuo
M
D000595:Amino Acid Sequence; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry*; D001665:Binding Sites; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D017706:Lisinopril / Q000737:chemistry*; D020780:Matrix Metalloproteinase 9 / Q000737:chemistry*; D008958:Models, Molecular
D000806:Angiotensin-Converting Enzyme Inhibitors; D017706:Lisinopril; D020780:Matrix Metalloproteinase 9