 |
PDBsum entry 1pjs
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Transferase/oxidoreductase/lyase
|
PDB id
|
|
|
|
1pjs
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Cysg structure reveals tetrapyrrole-Binding features and novel regulation of siroheme biosynthesis.
|
|
|
Authors
|
|
M.E.Stroupe,
H.K.Leech,
D.S.Daniels,
M.J.Warren,
E.D.Getzoff.
|
|
|
Ref.
|
|
Nat Struct Biol, 2003,
10,
1064-1073.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Sulfur metabolism depends on the iron-containing porphinoid siroheme. In
Salmonella enterica, the S-adenosyl-L-methionine (SAM)-dependent
bismethyltransferase, dehydrogenase and ferrochelatase, CysG, synthesizes
siroheme from uroporphyrinogen III (uro'gen III). The reactions mediated by CysG
encompass two branchpoint intermediates in tetrapyrrole biosynthesis, diverting
flux first from protoporphyrin IX biosynthesis and then from cobalamin (vitamin
B(12)) biosynthesis. We determined the first structure of this multifunctional
siroheme synthase by X-ray crystallography. CysG is a homodimeric gene fusion
product containing two structurally independent modules: a bismethyltransferase
and a dual-function dehydrogenase-chelatase. The methyltransferase active site
is a deep groove with a hydrophobic patch surrounded by hydrogen bond donors.
This asymmetric arrangement of amino acids may be important in directing
substrate binding. Notably, our structure shows that CysG is a phosphoprotein.
From mutational analysis of the post-translationally modified serine, we suggest
a conserved role for phosphorylation in inhibiting dehydrogenase activity and
modulating metabolic flux between siroheme and cobalamin pathways.
|
|
|
|
|
|
|
|
Figure 1.
Figure 1. Siroheme biosynthesis and its relationship to
cobalamin (vitamin B[12]) and protoporphyrin IX-derived
macrocycles (heme and chlorophyll).
|
|
Figure 5.
Figure 5. A stereo view of the methyltransferase active site
from the native CysG structure, which sits deep within a cleft
between the domains IA and IIA. (a) SAH (green) remains bound
in the active site during purification and crystallization.
Residues that bind SAH and that form the hydrophobic platform in
the center of the active site are purple. Atoms are colored as
in Figure 3. (b) The methyltransferase active site is an
asymmetric slot with charged residues (blue) circling a
hydrophobic patch (purple). (c) A model of uro'gen III in the
CysGA active site. Uro'gen III is dark gray. This
tetrapyrrole-binding model demonstrates the relationship among
residues we know to be important for the methyltransferase
reaction in the context of bound substrate. Same view as in b.
The reactive pyrrole group is marked with an asterisk.
|
|
|
|
|
|
The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2003,
10,
1064-1073)
copyright 2003.
|
|
|
|
|
|
|
