Capturing LTA₄ hydrolase in action: Insights to the chemistry and dynamics of chemotactic LTB₄ synthesis.

ABSTRACT: Human leukotriene (LT) A₄ hydrolase/aminopeptidase (LTA₄H) is a bifunctional enzyme that converts the highly unstable epoxide intermediate LTA₄ into LTB₄, a potent leukocyte activating agent, while the aminopeptidase activity cleaves and inactivates the chemotactic tripeptide Pro-Gly-Pro. Here, we describe high-resolution crystal structures of LTA₄H complexed with LTA₄, providing the structural underpinnings of the enzyme's unique epoxide hydrolase (EH) activity, involving Zn²⁺, Y383, E271, D375, and two catalytic waters. The structures reveal that a single catalytic water is involved in both catalytic activities of LTA₄H, alternating between epoxide ring opening and peptide bond hydrolysis, assisted by

SUBMITTER: Stsiapanava A 

PROVIDER: S-EPMC5594697 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature