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Hydrolase/hydrolase inhibitor
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PDB id
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1wqv
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Contents |
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142 a.a.
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254 a.a.
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191 a.a.
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* Residue conservation analysis
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PDB id:
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| Name: |
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Hydrolase/hydrolase inhibitor
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Title:
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Human factor viia-tissue factor complexed with propylsulfona thr-met-p-aminobenzamidine
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Structure:
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Coagulation factor vii. Chain: l. Fragment: factor vii light chain. Synonym: serum prothrombin conversion accelerator, spca, proconvertin, eptacog alfa. Engineered: yes. Coagulation factor vii. Chain: h. Fragment: factor vii heavy chain.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell: cho. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Biol. unit:
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Trimer (from
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Resolution:
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2.50Å
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R-factor:
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0.218
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R-free:
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0.272
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Authors:
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S.Kadono,A.Sakamoto,Y.Kikuchi,M.Oh-Eda,N.Yabuta,T.Koga,K.Hat T.Shiraishi,M.Haramura,H.Kodama
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Key ref:
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S.Kadono
et al.
(2004).
Crystal structure of human factor VIIa/tissue factor in complex with peptide mimetic inhibitor.
Biochem Biophys Res Commun,
324,
1227-1233.
PubMed id:
DOI:
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Date:
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02-Oct-04
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Release date:
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02-Oct-05
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PROCHECK
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Headers
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References
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P08709
(FA7_HUMAN) -
Coagulation factor VII
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Seq:
Struc:
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466 a.a.
142 a.a.*
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Enzyme class:
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Chains L, H:
E.C.3.4.21.21
- Coagulation factor VIIa.
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Reaction:
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Hydrolyzes one Arg-|-Ile bond in factor X to form factor Xa.
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Gene Ontology (GO) functional annotation
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Cellular component
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extracellular region
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2 terms
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Biological process
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blood coagulation
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2 terms
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Biochemical function
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catalytic activity
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4 terms
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DOI no:
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Biochem Biophys Res Commun
324:1227-1233
(2004)
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PubMed id:
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Crystal structure of human factor VIIa/tissue factor in complex with peptide mimetic inhibitor.
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S.Kadono,
A.Sakamoto,
Y.Kikuchi,
M.Oh-eda,
N.Yabuta,
T.Koga,
K.Hattori,
T.Shiraishi,
M.Haramura,
H.Kodama,
T.Esaki,
H.Sato,
Y.Watanabe,
S.Itoh,
M.Ohta,
T.Kozono.
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ABSTRACT
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The 3D structure of human factor VIIa/soluble tissue factor in complex with a
peptide mimetic inhibitor, propylsulfonamide-D-Thr-Met-p-aminobenzamidine, is
determined by X-ray crystallography. As compared with the interactions between
thrombin and thrombin inhibitors, the interactions at S2 and S3 sites
characteristic of factor VIIa and factor VIIa inhibitors are revealed. The S2
site has a small pocket, which is filled by the hydrophobic methionine side
chain in P2. The small S3 site fits the small size residue, D-threonine in P3.
The structural data and SAR data of the peptide mimetic inhibitor show that
these interactions in the S2 and S3 sites play an important role for the
improvement of selectivity versus thrombin. The results will provide valuable
information for the structure-based drug design of specific inhibitors for
FVIIa/TF.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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T.Shiraishi,
S.Kadono,
M.Haramura,
H.Kodama,
Y.Ono,
H.Iikura,
T.Esaki,
T.Koga,
K.Hattori,
Y.Watanabe,
A.Sakamoto,
K.Yoshihashi,
T.Kitazawa,
K.Esaki,
M.Ohta,
H.Sato,
and
T.Kozono
(2010).
Design and synthesis of peptidomimetic factor VIIa inhibitors.
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Chem Pharm Bull (Tokyo), 58,
38-44.
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R.Krishnan,
P.L.Kotian,
P.Chand,
S.Bantia,
S.Rowland,
and
Y.S.Babu
(2007).
Probing the S2 site of factor VIIa to generate potent and selective inhibitors: the structure of BCX-3607 in complex with tissue factor-factor VIIa.
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Acta Crystallogr D Biol Crystallogr, 63,
689-697.
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S.Kadono,
A.Sakamoto,
Y.Kikuchi,
M.Oh-Eda,
N.Yabuta,
T.Koga,
K.Hattori,
T.Shiraishi,
M.Haramura,
H.Kodama,
Y.Ono,
T.Esaki,
H.Sato,
Y.Watanabe,
S.Itoh,
M.Ohta,
and
T.Kozono
(2005).
Structure of human factor VIIa/tissue factor in complex with a peptide-mimetic inhibitor: high selectivity against thrombin by introducing two charged groups in P2 and P4.
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Acta Crystallogr Sect F Struct Biol Cryst Commun, 61,
169-173.
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PDB code:
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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
code is
shown on the right.
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Links
