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PDBsum entry 3ba0
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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 full-length human mmp-12
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Structure:
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Macrophage metalloelastase. Chain: a. Synonym: hme, matrix metalloproteinase-12, mmp-12, macrophage elastase, me. Engineered: yes. Mutation: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: mmp12, hme. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Resolution:
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3.00Å
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R-factor:
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0.243
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R-free:
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0.319
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Authors:
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I.Bertini,V.Calderone,M.Fragai,R.Jaiswal,C.Luchinat,M.Melikian, E.Myonas,D.I.Svergun
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Key ref:
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I.Bertini
et al.
(2008).
Evidence of reciprocal reorientation of the catalytic and hemopexin-like domains of full-length MMP-12.
J Am Chem Soc,
130,
7011-7021.
PubMed id:
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Date:
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07-Nov-07
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Release date:
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29-Jul-08
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PROCHECK
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Headers
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References
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P39900
(MMP12_HUMAN) -
Macrophage metalloelastase from Homo sapiens
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Seq:
Struc:
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470 a.a.
365 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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*
PDB and UniProt seqs differ
at 1 residue position (black
cross)
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Enzyme class:
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E.C.3.4.24.65
- macrophage elastase.
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Reaction:
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Hydrolysis of soluble and insoluble elastin. Specific cleavages are also produced at 14-Ala-|-Leu-15 and 16-Tyr-|-Leu-17 in the B chain of insulin.
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Cofactor:
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Ca(2+); Zn(2+)
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J Am Chem Soc
130:7011-7021
(2008)
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PubMed id:
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Evidence of reciprocal reorientation of the catalytic and hemopexin-like domains of full-length MMP-12.
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I.Bertini,
V.Calderone,
M.Fragai,
R.Jaiswal,
C.Luchinat,
M.Melikian,
E.Mylonas,
D.I.Svergun.
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ABSTRACT
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The proteolytic activity of matrix metalloproteinases toward extracellular
matrix components (ECM), cytokines, chemokines, and membrane receptors is
crucial for several homeostatic and pathological processes. Active MMPs are a
family of single-chain enzymes (23 family members in the human genome), most of
which constituted by a catalytic domain and by a hemopexin-like domain connected
by a linker. The X-ray structures of MMP-1 and MMP-2 suggest a conserved and
well-defined spatial relationship between the two domains. Here we present
structural data for MMP-12, suitably stabilized against self-hydrolysis, both in
solution (NMR and SAXS) and in the solid state (X-ray), showing that the
hemopexin-like and the catalytic domains experience conformational freedom with
respect to each other on a time scale shorter than 10(-8) s. Hints on the
probable conformations are also obtained. This experimental finding opens new
perspectives for the often hypothesized active role of the hemopexin-like domain
in the enzymatic activity of MMPs.
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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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E.Babini,
I.Bertini,
V.Borsi,
V.Calderone,
X.Hu,
C.Luchinat,
and
G.Parigi
(2011).
Structural characterization of human S100A16, a low-affinity calcium binder.
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J Biol Inorg Chem,
16,
243-256.
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PDB codes:
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A.Grishaev,
L.Guo,
T.Irving,
and
A.Bax
(2010).
Improved fitting of solution X-ray scattering data to macromolecular structures and structural ensembles by explicit water modeling.
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J Am Chem Soc,
132,
15484-15486.
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D.I.Svergun
(2010).
Small-angle X-ray and neutron scattering as a tool for structural systems biology.
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Biol Chem,
391,
737-743.
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P.Bernadó
(2010).
Effect of interdomain dynamics on the structure determination of modular proteins by small-angle scattering.
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Eur Biophys J,
39,
769-780.
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I.Bertini,
M.Fragai,
C.Luchinat,
M.Melikian,
and
C.Venturi
(2009).
Characterisation of the MMP-12-elastin adduct.
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Chemistry,
15,
7842-7845.
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I.Bertini,
M.Fragai,
C.Luchinat,
M.Melikian,
E.Mylonas,
N.Sarti,
and
D.I.Svergun
(2009).
Interdomain Flexibility in Full-length Matrix Metalloproteinase-1 (MMP-1).
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J Biol Chem,
284,
12821-12828.
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J.L.Lauer-Fields,
M.J.Chalmers,
S.A.Busby,
D.Minond,
P.R.Griffin,
and
G.B.Fields
(2009).
Identification of specific hemopexin-like domain residues that facilitate matrix metalloproteinase collagenolytic activity.
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J Biol Chem,
284,
24017-24024.
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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
codes are
shown on the right.
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Links
