 |
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
|
|
|
|
|
|
Enzyme class:
|
|
E.C.3.5.4.16
- Gtp cyclohydrolase i.
|
|
|
|
|
|
|
Pathway:
|
|
Folate Biosynthesis (early stages)
|
|
|
|
|
|
Reaction:
|
|
GTP + H2O = formate + 2-amino-4-hydroxy-6-(erythro-1,2,3- trihydroxypropyl)-dihydropteridine triphosphate
|
|
|
|
|
|
GTP
|
+
|
H(2)O
|
=
|
formate
|
+
|
2-amino-4-hydroxy-6-(erythro-1,2,3- trihydroxypropyl)-dihydropteridine triphosphate
|
|
|
|
|
|
|
|
|
|
|
|
|
Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
|
|
|
|
|
|
|
|
|
|
|
Gene Ontology (GO) functional annotation
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Cellular component
|
cytoplasm
|
1 term
|
|
|
Biological process
|
one-carbon metabolic process
|
2 terms
|
|
|
Biochemical function
|
nucleotide binding
|
6 terms
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
|
| |
|
DOI no:
|
J Biochem (tokyo)
138:263-275
(2005)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Novel reaction mechanism of GTP cyclohydrolase I. High-resolution X-ray crystallography of Thermus thermophilus HB8 enzyme complexed with a transition state analogue, the 8-oxoguanine derivative.
|
|
Y.Tanaka,
N.Nakagawa,
S.Kuramitsu,
S.Yokoyama,
R.Masui.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
GTP cyclohydrolase I (GTPCH1) catalyzes the conversion of GTP to
dihydroneopterin 3'-triphosphate. We found that an 8-oxoguanine derivative of
GTP (8-oxo-GTP) strongly bound to GTPCH1 from Thermus thermophilus HB8 (tGTPCH1)
as a competitive inhibitor. The affinity of 8-oxo-GTP was three orders of
magnitude greater than that of GTP. These results suggest that 8-oxo-GTP is a
transition state analogue of GTPCH1. We have solved the X-ray crystal structures
of tGTPCH1 complexed with 8-oxo-GTP and 8-oxo-dGTP at 2.0 and 1.8 A resolution,
respectively, as well as the free form of the enzyme at 2.2 A resolution. In the
structure of tGTPCH1 complexed with 8-oxo-GTP or 8-oxo-dGTP, the oxygen atoms at
O8 of the 8-oxoguanine groups, together with residues Cys108, His111 and Cys179,
are coordinated to the zinc ion. The water molecule between Ndelta1 of His177
and N7 of 8-oxoguanine is conserved in both structures. These structural data
are in accordance with one of the proposed transition states. Superimpositioning
of the structures indicates the imidazole ring of His110 is rotated, implying
concomitant proton transfer to the ribose ring O4'. Based on these structural
data we propose a novel reaction mechanism for GTPCH1.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Literature references that cite this PDB file's key reference
|
|
|
| |
PubMed id
|
|
Reference
|
|
|
|
|
|
B.Sankaran,
S.A.Bonnett,
K.Shah,
S.Gabriel,
R.Reddy,
P.Schimmel,
D.A.Rodionov,
V.de Crécy-Lagard,
J.D.Helmann,
D.Iwata-Reuyl,
and
M.A.Swairjo
(2009).
Zinc-independent folate biosynthesis: genetic, biochemical, and structural investigations reveal new metal dependence for GTP cyclohydrolase IB.
|
| |
J Bacteriol, 191,
6936-6949.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
C.Bolin,
and
F.Cardozo-Pelaez
(2009).
Characterization of oxidized guanosine 5'-triphosphate as a viable inhibitor of soluble guanylyl cyclase.
|
| |
Free Radic Biol Med, 46,
828-835.
|
|
|
|
|
|
|
P.Hänzelmann,
and
H.Schindelin
(2006).
Binding of 5'-GTP to the C-terminal FeS cluster of the radical S-adenosylmethionine enzyme MoaA provides insights into its mechanism.
|
| |
Proc Natl Acad Sci U S A, 103,
6829-6834.
|
|
|
PDB codes:
|
|
|
|
|
|
|
The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
|
|
Links
