This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

1oo9

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 07:12, 9 December 2020

Orientation in Solution of MMP-3 Catalytic Domain and N-TIMP-1 from Residual Dipolar Couplings

Structural highlights

1oo9 is a 2 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1uea
Gene:	MMP3 OR STMY1 (HUMAN), TIMP1 OR TIMP OR CLGI (HUMAN)
Activity:	Stromelysin 1, with EC number 3.4.24.17
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[MMP3_HUMAN] Defects in MMP3 are the cause of susceptibility to coronary heart disease type 6 (CHDS6) [MIM:614466]. A multifactorial disease characterized by an imbalance between myocardial functional requirements and the capacity of the coronary vessels to supply sufficient blood flow. Decreased capacity of the coronary vessels is often associated with thickening and loss of elasticity of the coronary arteries. Note=A polymorphism in the MMP3 promoter region is associated with the risk of coronary heart disease and myocardial infarction, due to lower MMP3 proteolytic activity and higher extracellular matrix deposition in atherosclerotic lesions.^[1] ^[2]

Function

[MMP3_HUMAN] Can degrade fibronectin, laminin, gelatins of type I, III, IV, and V; collagens III, IV, X, and IX, and cartilage proteoglycans. Activates procollagenase. [TIMP1_HUMAN] Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor. Also mediates erythropoiesis in vitro; but, unlike IL-3, it is species-specific, stimulating the growth and differentiation of only human and murine erythroid progenitors. Known to act on MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-11, MMP-12, MMP-13 and MMP-16. Does not act on MMP-14.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Crystal structures of catalytic domains of MMP-3 and MT1-MMP bound to TIMP-1 or TIMP-2, respectively, differ in the orientation of the TIMP in the MMP active site. The orientation in solution of N-TIMP-1 in the MMP-3 active site has been investigated using residual dipolar couplings (RDCs). Fitting of the RDCs to the X-ray structures of the complexes suggests general agreement with the orientation of crystalline MMP-3(DeltaC) and TIMP-1 and a large disparity from the orientation of crystalline MT1-MMP(DeltaC) and TIMP-2. Rigid body docking of MMP-3 and N-TIMP-1 X-ray coordinates using RDCs and intermolecular NOEs provided a time-averaged orientation in solution differing from the crystal structure by a 5 degrees rotation toward the MT1-MMP(DeltaC)/TIMP-2 orientation. The slight discrepancy in orientations in solution and crystal lies within the experimental uncertainties. Intermolecular NOEs used in the docking corroborated the accuracy of mapping the interface by a paramagnetic NMR footprinting assay, a potential alternative source of contacts for docking. Some uncertainty in the N-TIMP-1 orientation in the MMP-3 active site, coupled with microsecond to millisecond fluctuations of the MMP-binding ridge of N-TIMP-1 in the complex and flexibility in MMP-3(DeltaC) S(1)' to S(3)' subsites, leaves open the possibility that N-TIMP-1 might dynamically pivot a few degrees or more in the arc toward the MT1-MMP(DeltaC)/TIMP-2 orientation. Differing TIMP orientations in MMP active sites are more likely to result from structural differences in TIMP AB hairpin loops than from crystal packing artifacts.

Global orientation of bound MMP-3 and N-TIMP-1 in solution via residual dipolar couplings.,Arumugam S, Van Doren SR Biochemistry. 2003 Jul 8;42(26):7950-8. PMID:12834347^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ye S, Eriksson P, Hamsten A, Kurkinen M, Humphries SE, Henney AM. Progression of coronary atherosclerosis is associated with a common genetic variant of the human stromelysin-1 promoter which results in reduced gene expression. J Biol Chem. 1996 May 31;271(22):13055-60. PMID:8662692
↑ Yamada Y, Izawa H, Ichihara S, Takatsu F, Ishihara H, Hirayama H, Sone T, Tanaka M, Yokota M. Prediction of the risk of myocardial infarction from polymorphisms in candidate genes. N Engl J Med. 2002 Dec 12;347(24):1916-23. PMID:12477941 doi:10.1056/NEJMoa021445
↑ Arumugam S, Van Doren SR. Global orientation of bound MMP-3 and N-TIMP-1 in solution via residual dipolar couplings. Biochemistry. 2003 Jul 8;42(26):7950-8. PMID:12834347 doi:http://dx.doi.org/10.1021/bi034545s

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1oo9"

@@ Line 1: / Line 1: @@
 ==Orientation in Solution of MMP-3 Catalytic Domain and N-TIMP-1 from Residual Dipolar Couplings==
-<StructureSection load='1oo9' size='340' side='right' caption='[[1oo9]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''>
+<StructureSection load='1oo9' size='340' side='right'caption='[[1oo9]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1oo9]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OO9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1OO9 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1oo9]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OO9 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1OO9 FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1uea|1uea]]</td></tr>
+</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1uea|1uea]]</div></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MMP3 OR STMY1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), TIMP1 OR TIMP OR CLGI ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Stromelysin_1 Stromelysin 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.17 3.4.24.17] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1oo9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1oo9 OCA], [http://pdbe.org/1oo9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1oo9 RCSB], [http://www.ebi.ac.uk/pdbsum/1oo9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1oo9 ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1oo9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1oo9 OCA], [http://pdbe.org/1oo9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1oo9 RCSB], [http://www.ebi.ac.uk/pdbsum/1oo9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1oo9 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 32: / Line 32: @@
 </div>
 <div class="pdbe-citations 1oo9" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Matrix metalloproteinase 3D structures|Matrix metalloproteinase 3D structures]]
 == References ==
 <references/>
@@ Line 37: / Line 40: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Stromelysin 1]]
 [[Category: Arumugam, S]]

1oo9

From Proteopedia

Revision as of 07:12, 9 December 2020

Orientation in Solution of MMP-3 Catalytic Domain and N-TIMP-1 from Residual Dipolar Couplings

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox