Interaction of amiloride and one of its derivatives with Vpu from HIV-1: a molecular dynamics simulation.
Vpu is an 81-residue membrane protein, with a single transmembrane segment that is encoded by HIV-1 and is involved in the enhancement of virion release via formation of an ion channel. Cyclohexamethylene amiloride (Hma) has been shown to inhibit ion channel activity. In the present 12-ns simulation study a putative binding site of Hma blockers in a pentameric model bundle built of parallel aligned helices of the first 32 residues of Vpu was found near Ser-23. Hma orientates along the channel axis with its alkyl ring pointing inside the pore, which leads to a blockage of the pore.
Lemaitre
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V
Biomembrane Structure Unit, Department of Biochemistry, Oxford University, South Parks Road, Oxford OX1 3QU, UK.
Ali
R
R
Kim
C G
CG
Watts
A
A
Fischer
W B
WB
D000584:Amiloride / Q000378:metabolism*; D000595:Amino Acid Sequence; D001665:Binding Sites; D003198:Computer Simulation; D004347:Drug Interactions; D015497:HIV-1 / Q000737:chemistry*; D054298:Human Immunodeficiency Virus Proteins; D006860:Hydrogen Bonding; D007473:Ion Channels / Q000737:chemistry; D008956:Models, Chemical; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D011522:Protons; D012694:Serine / Q000737:chemistry; D013997:Time Factors; D054334:Viral Regulatory and Accessory Proteins / Q000737:chemistry* / Q000378:metabolism*; D000086082:Viroporin Proteins
D000584:Amiloride; D054298:Human Immunodeficiency Virus Proteins; D007473:Ion Channels; D011522:Protons; D012694:Serine; D054334:Viral Regulatory and Accessory Proteins; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins