ATPases as drug targets: learning from their structure.
ATPases are involved in several cellular functions, and are at the origin of various human diseases. They are therefore attractive drug targets, and various ATPase inhibitors are already on the market. However, most of these drugs are active without binding directly to the nucleotide-binding site. An alternative strategy to inhibit ATPases is to design competitive ATP inhibitors. This approach, which has been used successfully to design protein-kinase inhibitors, depends on the structure of the nucleotide-binding site. This review describes the structural features of the nucleotide-binding site of various ATPases and analyses how this structural information can be exploited for drug discovery.
Chène
Patrick
P
Oncology Department, Novartis, K125 442, CH-4002 Basel, Switzerland. patrick_chene@yahoo.com
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology; D015195:Drug Design; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D000251:Adenosine Triphosphatases