title: Examination of matrix metalloproteinase-1 in solution: a preference for the pre-collagenolysis state.
abstract: Catalysis of collagen degradation by matrix metalloproteinase 1 (MMP-1) has been proposed to critically rely on flexibility between the catalytic (CAT) and hemopexin-like (HPX) domains. A rigorous assessment of the most readily accessed conformations in solution is required to explain the onset of substrate recognition and collagenolysis. The present study utilized paramagnetic NMR spectroscopy and small angle x-ray scattering (SAXS) to calculate the maximum occurrence (MO) of MMP-1 conformations. The MMP-1 conformations with large MO values (up to 47%) are restricted into a relatively small conformational region. All conformations with high MO values differ largely from the closed MMP-1 structures obtained by x-ray crystallography. The MO of the latter is ~20%, which represents the upper limit for the presence of this conformation in the ensemble sampled by the protein in solution. In all the high MO conformations, the CAT and HPX domains are not in tight contact, and the residues of the HPX domain reported to be responsible for the binding to the collagen triple-helix are solvent exposed. Thus, overall analysis of the highest MO conformations indicated that MMP-1 in solution was poised to interact with collagen and then could readily proceed along the steps of collagenolysis.
authors.affiliation: From the CERM and.
authors.forename: Linda
authors.initials: L
authors.lastname: Cerofolini
authors.affiliation: the Torrey Pines Institute for Molecular Studies, Port St. Lucie, Florida 34987,. Electronic address: gfields@tpims.org.
authors.forename: Gregg B
authors.initials: GB
authors.lastname: Fields
authors.affiliation: From the CERM and; the Department of Chemistry "U. Schiff," University of Florence, Via Luigi Sacconi 6, 50019 Sesto Fiorentino (FI), Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Fragai
authors.affiliation: the Center for Neuroscience and Cell Biology and; the Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, P.O. Box 3046, 3001-401 Coimbra, Portugal, and.
authors.forename: Carlos F G C
authors.initials: CFGC
authors.lastname: Geraldes
authors.affiliation: From the CERM and; the Department of Chemistry "U. Schiff," University of Florence, Via Luigi Sacconi 6, 50019 Sesto Fiorentino (FI), Italy,. Electronic address: claudioluchinat@cerm.unifi.it.
authors.forename: Claudio
authors.initials: C
authors.lastname: Luchinat
authors.affiliation: From the CERM and; the Department of Chemistry "U. Schiff," University of Florence, Via Luigi Sacconi 6, 50019 Sesto Fiorentino (FI), Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Parigi
authors.affiliation: From the CERM and; the Department of Chemistry "U. Schiff," University of Florence, Via Luigi Sacconi 6, 50019 Sesto Fiorentino (FI), Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Ravera
authors.affiliation: the EMBL, c/o DESY, Notkestrasse 85, Geb. 25 A, 22603 Hamburg, Germany.
authors.forename: Dmitri I
authors.initials: DI
authors.lastname: Svergun
authors.affiliation: From the CERM and; the Center for Neuroscience and Cell Biology and; the Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, P.O. Box 3046, 3001-401 Coimbra, Portugal, and.
authors.forename: João M C
authors.initials: JMC
authors.lastname: Teixeira
mesh_terms: D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000737:chemistry* / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D053838:Scattering, Small Angle
chemical_list: C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1
keywords: Chemical Biology; Collagen; Collagenolysis; Matrix Metalloproteinase (MMP); Maximum Occurrence; Metalloprotease; Structural Biology
references.citation: J Am Chem Soc. 2010 Sep 29;132(38):13553-8
references.pmid: 20822180
references.citation: J Biomol NMR. 2011 Sep;51(1-2):131-50
references.pmid: 21947922
references.citation: J Biomol NMR. 2004 Jul;29(3):339-49
references.pmid: 15213432
references.citation: Curr Biol. 2012 Jun 19;22(12):1047-56
references.pmid: 22578418
references.citation: J Am Chem Soc. 2012 Feb 1;134(4):2100-10
references.pmid: 22239621
references.citation: J Am Chem Soc. 2008 May 21;130(20):6395-403
references.pmid: 18439013
references.citation: J Biol Chem. 2009 May 8;284(19):12821-8
references.pmid: 19282283
references.citation: J Am Chem Soc. 2007 Mar 21;129(11):3315-27
references.pmid: 17319663
references.citation: Proc Natl Acad Sci U S A. 2005 Nov 22;102(47):17002-7
references.pmid: 16284250
references.citation: Biochemistry. 2003 Jul 8;42(26):8011-21
references.pmid: 12834353
references.citation: J Magn Reson. 2004 Apr;167(2):228-41
references.pmid: 15040978
references.citation: Phys Chem Chem Phys. 2012 Jul 7;14(25):9149-56
references.pmid: 22622816
references.citation: FEBS Lett. 2012 Mar 9;586(5):557-67
references.pmid: 21945315
references.citation: J Biol Chem. 2002 Jul 26;277(30):27378-84
references.pmid: 12011042
references.citation: J Biol Chem. 2005 Mar 11;280(10):9578-85
references.pmid: 15611040
references.citation: Anal Biochem. 2000 Aug 1;283(2):153-8
references.pmid: 10906235
references.citation: J Magn Reson. 2012 Feb;215:85-93
references.pmid: 22264683
references.citation: J Am Chem Soc. 2007 May 2;129(17):5656-64
references.pmid: 17411046
references.citation: Mol Biotechnol. 2002 Sep;22(1):51-86
references.pmid: 12353914
references.citation: J Biol Chem. 2011 Dec 30;286(52):45073-82
references.pmid: 22030392
references.citation: J Am Chem Soc. 2008 Aug 13;130(32):10486-7
references.pmid: 18642818
references.citation: J Biomol NMR. 2012 Aug;53(4):271-80
references.pmid: 22639196
references.citation: J Am Chem Soc. 2008 Nov 5;130(44):14802-12
references.pmid: 18826316
references.citation: Bioinformatics. 2003 Oct;19 Suppl 2:ii246-55
references.pmid: 14534198
references.citation: J Am Chem Soc. 2008 Jun 4;130(22):7011-21
references.pmid: 18465858
references.citation: Angew Chem Int Ed Engl. 2006 Dec 4;45(47):7952-5
references.pmid: 17096442
references.citation: J Biol Chem. 2004 Oct 8;279(41):43336-44
references.pmid: 15292230
references.citation: EMBO J. 2004 Aug 4;23(15):3020-30
references.pmid: 15257288
references.citation: J Med Chem. 2005 Dec 1;48(24):7544-59
references.pmid: 16302796
references.citation: J Biol Chem. 2013 Mar 29;288(13):8785-93
references.pmid: 23430258
references.citation: J Am Chem Soc. 2010 Jan 13;132(1):241-7
references.pmid: 19961227
references.citation: J Biol Inorg Chem. 2012 Apr;17(4):663-72
references.pmid: 22407541
references.citation: Proc Natl Acad Sci U S A. 2004 May 4;101(18):6841-6
references.pmid: 15100408
references.citation: Structure. 1995 Jun 15;3(6):541-9
references.pmid: 8590015
references.citation: Science. 2008 Jun 13;320(5882):1471-5
references.pmid: 18556554
references.citation: Nature. 2006 Apr 27;440(7088):1227-30
references.pmid: 16642002
references.citation: Structure. 2007 Oct;15(10):1159-61
references.pmid: 17937904
references.citation: Structure. 2007 Oct;15(10):1227-36
references.pmid: 17937912
references.citation: J Am Chem Soc. 2003 Nov 5;125(44):13338-9
references.pmid: 14583012
references.citation: Nature. 2007 Dec 20;450(7173):1263-7
references.pmid: 18097416
references.citation: J Biol Chem. 2009 Sep 4;284(36):24017-24
references.pmid: 19574232
references.citation: Nature. 2006 Nov 16;444(7117):383-6
references.pmid: 17051159
references.citation: Proc Natl Acad Sci U S A. 2006 Dec 12;103(50):18945-50
references.pmid: 17146057
references.citation: J Am Chem Soc. 2007 Oct 24;129(42):12786-94
references.pmid: 17910448
references.citation: J Am Chem Soc. 2011 Nov 23;133(46):18966-74
references.pmid: 21999431
references.citation: Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12461-6
references.pmid: 22761315
references.citation: J Am Chem Soc. 2001 Feb 21;123(7):1416-24
references.pmid: 11456715
references.citation: J Mol Biol. 2006 Sep 8;362(1):78-88
references.pmid: 16890240
references.citation: Structure. 2012 Mar 7;20(3):522-33
references.pmid: 22405011
references.citation: Biochemistry. 2007 Mar 27;46(12):3724-33
references.pmid: 17338550
references.citation: Nature. 2005 Jan 13;433(7022):128-32
references.pmid: 15650731
references.citation: J Mol Biol. 2009 Jan 16;385(2):665-74
references.pmid: 18996395
references.citation: Angew Chem Int Ed Engl. 2004 Apr 19;43(17):2254-6
references.pmid: 15108136
references.citation: J Magn Reson. 2010 Nov;207(1):8-16
references.pmid: 20829084
references.citation: J Appl Crystallogr. 2012 Mar 15;45(Pt 2):342-350
references.pmid: 25484842
references.citation: Science. 2004 Oct 1;306(5693):108-11
references.pmid: 15459390
references.citation: J Magn Reson. 2009 Nov;201(1):25-33
references.pmid: 19700353
references.citation: J Biomol NMR. 2011 Nov;51(3):253-63
references.pmid: 21826520
references.citation: J Mol Biol. 2013 May 27;425(10):1815-25
references.pmid: 23399546