Jekyll and Hyde: motion may explain similar enzymes’ divergence

Posted on August 23, 2013
YopH and PTP1B Enzymes

YopH and PTP1B Enzymes
Two ribbon diagrams depict two very similar enzymes: YopH in cyan and PTP1B in gray. Though virtually identical in structure, the two enzymes serve very different purposes. Utah State University chemist Alvan Hengge, with colleagues from Yale University, are uncovering the subtle differences and report their findings in the Aug. 23 issue of the journal Science. Image courtesy Yale University.

One enzyme regulates the body’s insulin receptor, ensuring energy needed for function and survival. The other enables a bacterium to wreak havoc in the form of bubonic plague.

“Their purposes in life couldn’t be more different,” says Utah State University chemist Alvan Hengge.

From a molecular standpoint, the two enzymes appear virtually identical. Yet, they catalyze the same reaction at very different rates.

With colleagues Sean Whittier and Patrick Loria of Yale University, Hengge, who has puzzled over this ‘Jekyll-Hyde’ conundrum for several years, published findings that may explain the dissimilarities in the Aug. 23, 2013, issue of Science. The research was supported by funding from the National Institutes of Health and the National Science Foundation.

“We’ve known since the 1990s that molecular motions in the class of enzymes called protein tyrosine phosphatases are crucial for their optimal function,” says Hengge, professor and head of USU’s Department of Chemistry and Biochemistry. “What we’re discovering is the speed of these motions is different among PTPs and is the reason some of them are much faster catalysts than others.”

Using nuclear magnetic resonance, the team compared the active-site loop motions in two structurally similar enzymes. One, PTP1B, is the human phosphatase involved in regulation of the insulin receptor, as well as leptin and epidermal growth factor signaling. The other, YopH, is the virulence factor from the bacterium Yersinia, an invasive pathogen that causes life-threatening infection.

Read more at: Phys.org