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PDBsum entry 4gwn
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PDB id:
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Hydrolase
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Title:
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Crystal structure of human mature meprin beta
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Structure:
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Meprin a subunit beta. Chain: a. Fragment: mature meprin beta ectomoiety, unp residues 62-614. Synonym: endopeptidase-2, meprin b, n-benzoyl-l-tyrosyl-p-amino- benzoic acid hydrolase subunit beta, paba peptide hydrolase, pph beta. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: mep1b. Expressed in: trichoplusia ni. Expression_system_taxid: 7111.
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Resolution:
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3.00Å
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R-factor:
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0.198
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R-free:
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0.238
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Authors:
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J.L.Arolas,C.Broder,T.Jefferson,T.Guevara,E.E.Sterchi,W.Bode, W.Stocker,C.Becker-Pauly,F.X.Gomis-Ruth
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Key ref:
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J.L.Arolas
et al.
(2012).
Structural basis for the sheddase function of human meprin β metalloproteinase at the plasma membrane.
Proc Natl Acad Sci U S A,
109,
16131-16136.
PubMed id:
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Date:
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03-Sep-12
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Release date:
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19-Sep-12
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PROCHECK
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Headers
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References
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Q16820
(MEP1B_HUMAN) -
Meprin A subunit beta from Homo sapiens
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Seq:
Struc:
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701 a.a.
533 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.3.4.24.63
- meprin B.
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Reaction:
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Hydrolysis of proteins, including azocasein, and peptides. Hydrolysis of 5-His-|-Leu-6, 6-Leu-|-Cys-7, 14-Ala-|-Leu-15 and 19-Cys-|-Gly-20 bonds in insulin B chain.
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Cofactor:
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Zn(2+)
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Proc Natl Acad Sci U S A
109:16131-16136
(2012)
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PubMed id:
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Structural basis for the sheddase function of human meprin β metalloproteinase at the plasma membrane.
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J.L.Arolas,
C.Broder,
T.Jefferson,
T.Guevara,
E.E.Sterchi,
W.Bode,
W.Stöcker,
C.Becker-Pauly,
F.X.Gomis-Rüth.
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ABSTRACT
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Ectodomain shedding at the cell surface is a major mechanism to regulate the
extracellular and circulatory concentration or the activities of signaling
proteins at the plasma membrane. Human meprin β is a 145-kDa disulfide-linked
homodimeric multidomain type-I membrane metallopeptidase that sheds
membrane-bound cytokines and growth factors, thereby contributing to
inflammatory diseases, angiogenesis, and tumor progression. In addition, it
cleaves amyloid precursor protein (APP) at the β-secretase site, giving rise to
amyloidogenic peptides. We have solved the X-ray crystal structure of a major
fragment of the meprin β ectoprotein, the first of a multidomain oligomeric
transmembrane sheddase, and of its zymogen. The meprin β dimer displays a
compact shape, whose catalytic domain undergoes major rearrangement upon
activation, and reveals an exosite and a sugar-rich channel, both of which
possibly engage in substrate binding. A plausible structure-derived working
mechanism suggests that substrates such as APP are shed close to the plasma
membrane surface following an "N-like" chain trace.
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