Target Binding Site Detail

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Target General Information
Ligand General Information
Drug Binding Sites of Target
References
Target General Information  Top
Target ID T28226 Target Info
Target Name GTP cyclohydrolase-I (GCH1)
Synonyms Guanosine triphosphate cyclohydrolase I; GTP-CH-I; GTP cyclohydrolase I; GTP cyclohydrolase 1; GCH; DYT5
Target Type Clinical trial Target
Gene Name GCH1
Biochemical Class Carbon-nitrogen hydrolase
UniProt ID
GCH1_HUMAN
Ligand General Information  Top
Ligand Name 7,8-dihydrobiopterin Ligand Info
Canonical SMILES CC(C(C1=NC2=C(NC1)N=C(NC2=O)N)O)O
InChI 1S/C9H13N5O3/c1-3(15)6(16)4-2-11-7-5(12-4)8(17)14-9(10)13-7/h3,6,15-16H,2H2,1H3,(H4,10,11,13,14,17)/t3-,6-/m0/s1
InChIKey FEMXZDUTFRTWPE-DZSWIPIPSA-N
PubChem Compound ID 135398687
Drug Binding Sites of Target  Top
PDB ID: 6Z85      inhibitory human GTP cyclohydrolase I - GFRP complex
Method Electron microscopy Resolution 2.90 Å Mutation No [1]
PDB Sequence
NLPNLAAAYS
76
SILSSLGENP
86
QRQGLLKTPW
96
RAASAMQFFT
106
KGYDEMVIVK
133

DIDMFSMCEH
143
HLVPFVGKVH
153
IGYLPNKQVL
163
GLSKLARIVE
173
IYSRRLQVQE
183

RLTKQIAVAI
193
TEALRPAGVG
203
VVVEATHMCK
224
TVTSTMLGVF
234
REDPKTREEF
244

LTLIR
Residue
Distance (Å)
ASP127
3.210
GLU128
4.164
MET129
4.010
LEU157
3.659
VAL233
4.028
Residue
Distance (Å)
ASP237
3.493
LYS239
4.468
THR240
2.911
GLU243
2.415
PDB ID: 7ALQ      human GCH-GFRP inhibitory complex 7-deaza-GTP bound
Method X-ray diffraction Resolution 2.21 Å Mutation No [2]
PDB Sequence
PRSEEDNELN
67
LPNLAAAYSS
77
ILSSLGENPQ
87
RQGLLKTPWR
97
AASAMQFFTK
107

GYQETISDVL
117
NDAIFDEDHD
127
EMVIVKDIDM
137
FSMCEHHLVP
147
FVGKVHIGYL
157

PNKQVLGLSK
167
LARIVEIYSR
177
RLQVQERLTK
187
QIAVAITEAL
197
RPAGVGVVVE
207

ATHMCMVMRG
217
VQKMNSKTVT
227
STMLGVFRED
237
PKTREEFLTL
247
IR
Residue
Distance (Å)
ASP127
2.413
GLU128
3.328
MET129
3.358
LEU157
3.024
ASN159
4.590
ALA200
2.426
GLY201
4.680
SER228
2.005
THR229
3.637
Residue
Distance (Å)
MET230
3.482
VAL233
3.102
ARG235
2.270
ASP237
4.735
LYS239
4.945
THR240
2.677
ARG241
2.631
GLU243
1.779
References  Top
REF 1 A hybrid approach reveals the allosteric regulation of GTP cyclohydrolase I. Proc Natl Acad Sci U S A. 2020 Dec 15;117(50):31838-31849.
REF 2 Biophysical and structural investigation of the regulation of human GTP cyclohydrolase I by its regulatory protein GFRP. J Struct Biol. 2021 Mar;213(1):107691.

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