| Popis: |
KshAB is a Rieske oxygenase (RO) in the aerobic steroid degradation pathways of bacteria. It is a monooxygenase responsible for the 9α-hydroxylation of the nucleus of 3-keto-4-ene steroids bearing short side chains at C17. It is composed of two domains arranged in a head-to-tail fashion to form the functional trimer. The N-terminal Rieske domain harbors a Fe2S2 cluster in which the two irons are coordinated by two cysteine and two histidine residues, respectively. The larger, C-terminal catalytic domain contains a mononuclear nonheme iron coordinated by a His-His-Asp facial triad. Purified KshAB from Mycobacterium tuberculosis exhibits substrate specificities for 1,4-androstadien-3,17-one and dioxygen 2-3 orders of magnitude lower than those measured for other ROs and their best substrates. In agreement with the large fused-ring substrate, the structure of KshA incorporates an active site channel and substrate binding pocket that are longer than those observed in other ROs, and positioned in a different relative orientation within the catalytic domain. KshA also possesses a C-terminal helix which occupies a position not observed in other RO structures and which likely stabilizes trimeric quaternary structure. Finally, KshA exhibits a minimal core catalytic domain with respect to secondary structural elements that may prove archetypical for ROs. 3D Structure Keywords: Rieske; monooxygenase; mycobacterium tuberculosis steroid; cholesterol degradation; 9α-hydroxylation; KshA |
