Study catches picture of deadly cancer enzyme

Study catches picture of deadly cancer enzyme

Scientists have captured an image of an enzyme key to the progression of the deadliest cancers and said on Wednesday their findings may lead to new therapies against not only cancer, but HIV and diabetes too.

They caught in the act a mutant version of an enzyme called p300/CBP, which is involved in pancreatic, colon, and lung cancers, thyroid cancer and some leukemias.

The image of this structure might provide a way to design a drug that blocks it, and perhaps stop some tumor-causing mutations.

The same structure is involved in infection with the AIDS virus and diabetes, as well, said Dr. Philip Cole, a professor and director of pharmacology and molecular sciences at Johns Hopkins University in Baltimore.

"If we could wipe all those, we would have a lot fewer deaths," Cole said in a telephone interview.

Writing in the journal Nature, Cole and colleagues at the Wistar Institute and the University of Pennsylvania said the enzyme acted in a hit-and-run fashion, working so quickly it had been difficult to image it. Without an image, it is hard to know precisely how to counter its effects.

The enzyme p300/CBP is a transcription factor, one of a large family of enzymes that unwrap DNA from around other proteins known as histones.

Cole said a delicate balance of p300 was needed, as either too much or too little can both lead to cancer.

"There is definitely some evidence that blocking this enzyme in the host may make it harder for HIV to be pathogenic," Cole added.

His lab has a compound that interferes with p300 but now it may be possible to make a better one, he said.

"We've had a chemical inhibitor of p300 for about nine years now, but without the structure, we had no idea how it was working or, more importantly, how to improve on it," he said.

"We're still in our infancy of understanding how to go after cancer," Cole added. "But this definitely is a step in the right direction."

The study may also help explain how some natural products can affect cancer. Curcumin, the compound that makes the spice turmeric yellow, has been shown in studies to interfere with p300/CBP.