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PDBsum entry 3h0c
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Contents |
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* Residue conservation analysis
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PDB id:
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Hydrolase
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Title:
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Crystal structure of human dipeptidyl peptidase iv (cd26) in complex with a reversed amide inhibitor
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Structure:
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Dipeptidyl peptidase 4. Chain: a, b. Synonym: dipeptidyl peptidase iv, dpp iv, t-cell activation antigen cd26, tp103, adenosine deaminase complexing protein 2, adabp, dipeptidyl peptidase 4 membrane form, dipeptidyl peptidase iv membrane form, dipeptidyl peptidase 4 soluble form, dipeptidyl peptidase iv soluble form. Ec: 3.4.14.5
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Source:
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Homo sapiens. Human. Organism_taxid: 9606
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Resolution:
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2.66Å
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R-factor:
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0.206
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R-free:
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0.271
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Authors:
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S.Nordhoff,S.Cerezo-Galvez,H.Deppe,O.Hill,M.Lopez-Canet,C.Rummey, M.Thiemann,V.G.Matassa,P.J.Edwards,A.Feurer
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Key ref:
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S.Nordhoff
et al.
(2009).
Discovery of beta-homophenylalanine based pyrrolidin-2-ylmethyl amides and sulfonamides as highly potent and selective inhibitors of dipeptidyl peptidase IV.
Bioorg Med Chem Lett,
19,
4201-4203.
PubMed id:
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Date:
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09-Apr-09
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Release date:
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09-Jun-09
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PROCHECK
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Headers
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References
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P27487
(DPP4_HUMAN) -
Dipeptidyl peptidase 4 from Homo sapiens
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Seq:
Struc:
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766 a.a.
728 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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Enzyme class:
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E.C.3.4.14.5
- dipeptidyl-peptidase Iv.
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Reaction:
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Release of an N-terminal dipeptide, Xaa-Xbb-|-Xcc, from a polypeptide, preferentially when Xbb is Pro, provided Xcc is neither Pro nor hydroxyproline.
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Bioorg Med Chem Lett
19:4201-4203
(2009)
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PubMed id:
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Discovery of beta-homophenylalanine based pyrrolidin-2-ylmethyl amides and sulfonamides as highly potent and selective inhibitors of dipeptidyl peptidase IV.
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S.Nordhoff,
S.Cerezo-Gálvez,
H.Deppe,
O.Hill,
M.López-Canet,
C.Rummey,
M.Thiemann,
V.G.Matassa,
P.J.Edwards,
A.Feurer.
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ABSTRACT
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Modifications of DPP-4 inhibitor 5, that was discovered by structure based
design, are described and structure-activity relationships discussed. With
analogue 7k one of the most potent non-covalent inhibitors of DPP-4 reported to
date (IC(50)=0.38nM) was discovered. X-ray structure of inhibitor 7k bound to
DPP-4 revealed a hydrogen bonding interaction with Q553. First successful
efforts in balancing overall properties, as demonstrated by improved metabolic
stability, highlight the potential of this series.
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Links
