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PDBsum entry 2v4a
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Contents |
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182 a.a.
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187 a.a.
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194 a.a.
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References listed in PDB file
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Key reference
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Title
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The active site of an algal prolyl 4-Hydroxylase has a large structural plasticity.
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Authors
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M.K.Koski,
R.Hieta,
C.Böllner,
K.I.Kivirikko,
J.Myllyharju,
R.K.Wierenga.
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Ref.
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J Biol Chem, 2007,
282,
37112-37123.
[DOI no: ]
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PubMed id
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Abstract
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Prolyl 4-hydroxylases (P4Hs) are 2-oxoglutarate dioxygenases that catalyze the
hydroxylation of peptidyl prolines. They play an important role in collagen
synthesis, oxygen homeostasis, and plant cell wall formation. We describe four
structures of a P4H from the green alga Chlamydomonas reinhardtii, two of the
apoenzyme at 1.93 and 2.90A resolution, one complexed with the competitive
inhibitor Zn(2+), and one with Zn(2+) and pyridine 2,4-dicarboxylate (which is
an analogue of 2-oxoglutarate) at 1.85A resolution. The structures reveal the
double-stranded beta-helix core fold (jellyroll motif), typical for
2-oxoglutarate dioxygenases. The catalytic site is at the center of an extended
shallow groove lined by two flexible loops. Mutagenesis studies together with
the crystallographic data indicate that this groove participates in the binding
of the proline-rich peptide-substrates. It is discussed that the algal P4H and
the catalytic domain of collagen P4Hs have notable structural similarities,
suggesting that these enzymes form a separate structural subgroup of P4Hs
different from the hypoxia-inducible factor P4Hs. Key structural differences
between these two subgroups are described. These studies provide first insight
into the structure-function relationships of the collagen P4Hs, which unlike the
hypoxia-inducible factor P4Hs use proline-rich peptides as their substrates.
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Figure 1.
FIGURE 1. The reaction catalyzed by P4H (A) and the
structures of 2-oxoglutarate (B) and pyridine 2,4-dicarboxylate
(C). For consistency in nomenclature, the atoms in pyridine
2,4-dicarboxylate are shown using the same numbering as in
2-oxoglutarate.
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Figure 8.
FIGURE 8. Stereoviews of the superimposition of the
catalytic sites of the ternary structures of Cr-P4H-1,
HIF-P4H-2, and CAS. A, stereo view showing the active site of
the ternary structure of Cr-P4H-1 superimposed on that of
HIF-P4H-2 complexed with inhibitor and Fe^2+ (PDB code 2G19). B,
superimposition of the ternary Cr-P4H-1 active site with the CAS
active site complexed with Fe^2+ and 2-oxoglutarate in the
presence or absence of NO. The Cr-P4H-1 is shown with gray
carbons and bonds in both panels. In panel A HIF-P4H-2 and the
bound inhibitor are in cyan. In panel B CAS is shown in yellow,
whereas the two modes of binding of 2-oxoglutarate are in yellow
(in the complex without NO; PDB code 1DRY) and magenta (in the
complex with NO, PDB code 1GVG). The water molecules in the
active sites of HIF-P4H-2 (two waters) and CAS (one water in the
structure with NO) are shown in magenta.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2007,
282,
37112-37123)
copyright 2007.
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