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PDBsum entry 4jz1
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Hydrolase/hydrolase inhibitor
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PDB id
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4jz1
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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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Crystal structure of matriptase in complex with inhibitor
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Structure:
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Suppressor of tumorigenicity 14 protein. Chain: a. Fragment: unp residues 615-855. Synonym: matriptase, membrane-type serine protease 1, mt-sp1, prostamin, serine protease 14, serine protease tadg-15, tumor- associated differentially-expressed gene 15 protein. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: st14, prss14, snc19, tadg15. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Resolution:
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1.90Å
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R-factor:
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0.216
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R-free:
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0.241
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Authors:
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H.S.Subramanya,B.C.Ravi,K.N.Ashok,G.Chakshusmathi,K.S.Ramesh
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Key ref:
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R.Goswami
et al.
(2013).
Discovery of Pyridyl Bis(oxy)dibenzimidamide Derivatives as Selective Matriptase Inhibitors.
Acs Med Chem Lett,
4,
1152-1157.
PubMed id:
DOI:
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Date:
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02-Apr-13
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Release date:
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26-Feb-14
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PROCHECK
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Headers
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References
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Q9Y5Y6
(ST14_HUMAN) -
Suppressor of tumorigenicity 14 protein from Homo sapiens
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Seq:
Struc:
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855 a.a.
241 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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DOI no:
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Acs Med Chem Lett
4:1152-1157
(2013)
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PubMed id:
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Discovery of Pyridyl Bis(oxy)dibenzimidamide Derivatives as Selective Matriptase Inhibitors.
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R.Goswami,
S.Mukherjee,
G.Wohlfahrt,
C.Ghadiyaram,
J.Nagaraj,
B.R.Chandra,
R.K.Sistla,
L.K.Satyam,
D.S.Samiulla,
A.Moilanen,
H.S.Subramanya,
M.Ramachandra.
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ABSTRACT
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Matriptase belongs to trypsin-like serine proteases involved in matrix
remodeling/degradation, growth regulation, survival, motility, and cell
morphogenesis. Herein, we report a structure-based approach, which led to the
discovery of sulfonamide and amide derivatives of pyridyl bis(oxy)benzamidine as
potent and selective matriptase inhibitors. Co-crystal structures of selected
compounds in complex with matriptase supported compound designing. Additionally,
WaterMap analyses indicated the possibility of occupying a distinct pocket
within the catalytic domain, exploration of which resulted in >100-fold
improvement in potency. Co-crystal structure of 10 with matriptase revealed
critical interactions leading to potent target inhibition and selectivity
against other serine proteases.
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