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@ARTICLE{Myllykoski:168209,
author = {Myllykoski, Matti and Raasakka, Arne and Lehtimäki, Mari
and Han, Huijong and Kursula, Inari and Kursula, Petri},
title = {{C}rystallographic {A}nalysis of the {R}eaction {C}ycle of
2′,3′-{C}yclic {N}ucleotide 3′-{P}hosphodiesterase, a
{U}nique {M}ember of the 2{H} {P}hosphoesterase {F}amily},
journal = {Journal of molecular biology},
volume = {425},
number = {22},
issn = {0022-2836},
address = {Amsterdam [u.a.]},
publisher = {Elsevier},
reportid = {DESY-2014-02414},
pages = {4307 - 4322},
year = {2013},
note = {© Elsevier Ltd.; Post referee fulltext in progress;
Embargo 12 months from publication},
abstract = {2H phosphoesterases catalyze reactions on nucleotide
substrates and contain two conserved histidine residues in
the active site. Very limited information is currently
available on the details of the active site and
substrate/product binding during the catalytic cycle of
these enzymes. We performed a comprehensive X-ray
crystallographic study of mouse 2',3'-cyclic nucleotide
3'-phosphodiesterase (CNPase), a membrane-associated enzyme
present at high levels in the tetrapod myelin sheath. We
determined crystal structures of the CNPase
phosphodiesterase domain complexed with substrate, product,
and phosphorothioate analogues. The data provide detailed
information on the CNPase reaction mechanism, including
substrate binding mode and coordination of the nucleophilic
water molecule. Linked to the reaction, an open/close motion
of the β5-α7 loop is observed. The role of the N terminus
of helix α7--unique for CNPase in the 2H family--during the
reaction indicates that 2H phosphoesterases differ in their
respective reaction mechanisms despite the conserved
catalytic residues. Furthermore, based on small-angle X-ray
scattering, we present a model for the full-length enzyme,
indicating that the two domains of CNPase form an elongated
molecule. Finally, based on our structural data and a
comprehensive bioinformatics study, we discuss the
conservation of CNPase in various organisms.},
cin = {EMBL-User},
ddc = {570},
cid = {I:(DE-H253)EMBL-User-20120814},
pnm = {DORIS Beamline K1.1 (POF2-54G13) / PETRA Beamline P14
(POF2-54G14)},
pid = {G:(DE-H253)POF2-K1.1-20130405 /
G:(DE-H253)POF2-P14-20130405},
experiment = {EXP:(DE-H253)D-K1.1-20150101 / EXP:(DE-H253)P-P14-20150101},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000328100500023},
pubmed = {pmid:23831225},
doi = {10.1016/j.jmb.2013.06.012},
url = {https://bib-pubdb1.desy.de/record/168209},
}