5i12

From Proteopedia

(Difference between revisions)

Revision as of 08:40, 27 May 2020

Crystal structure of the catalytic domain of MMP-9 in complex with a selective sugar-conjugated arylsulfonamide carboxylate water-soluble inhibitor (DC27).

Structural highlights

5i12 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , , ,
Related:	5iol, 4hma
Gene:	MMP9, CLG4B (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[MMP9_HUMAN] Defects in MMP9 may be a cause of susceptibility to intervertebral disc disease (IDD) [MIM:603932]; also known as lumbar disk herniation (LDH). IDD is one of the most common musculo-skeletal disorders and the predominant cause of low-back pain and unilateral leg pain.^[1] Defects in MMP9 are the cause of metaphyseal anadysplasia type 2 (MANDP2) [MIM:613073]. Metaphyseal anadysplasia consists of an abnormal bone development characterized by severe skeletal changes that, in contrast with the progressive course of most other skeletal dysplasias, resolve spontaneously with age. Clinical characteristics are evident from the first months of life and include slight shortness of stature and a mild varus deformity of the legs. Patients attain a normal stature in adolescence and show improvement or complete resolution of varus deformity of the legs and rhizomelic micromelia.

Function

[MMP9_HUMAN] May play an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. Could play a role in bone osteoclastic resorption. Cleaves KiSS1 at a Gly-|-Leu bond. Cleaves type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. Degrades fibronectin but not laminin or Pz-peptide.^[2]

Publication Abstract from PubMed

Matrix metalloproteinase-12 (MMP-12) can be considered an attractive target to study selective inhibitors useful in the development of new therapies for lung and cardiovascular diseases. In this study, a new series of arylsulfonamide carboxylates, with increased hydrophilicity resulting from conjugation with a beta-N-acetyl-d-glucosamine moiety, were designed and synthesized as MMP-12 selective inhibitors. Their inhibitory activity was evaluated on human MMPs by using the fluorimetric assay, and a crystallographic analysis was performed to characterize their binding mode. Among these glycoconjugates, a nanomolar MMP-12 inhibitor with improved water solubility, compound 3 [(R)-2-(N-(2-(3-(2-acetamido-2-deoxy-beta-d-glucopyranosyl)thioureido)ethyl)biphe nyl-4-ylsulfonamido)-3-methylbutanoic acid], was identified.

Sugar-Based Arylsulfonamide Carboxylates as Selective and Water-Soluble Matrix Metalloproteinase-12 Inhibitors.,Nuti E, Cuffaro D, D'Andrea F, Rosalia L, Tepshi L, Fabbi M, Carbotti G, Ferrini S, Santamaria S, Camodeca C, Ciccone L, Orlandini E, Nencetti S, Stura EA, Dive V, Rossello A ChemMedChem. 2016 Jun 30. doi: 10.1002/cmdc.201600235. PMID:27356908^[3]

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

References

↑ Hirose Y, Chiba K, Karasugi T, Nakajima M, Kawaguchi Y, Mikami Y, Furuichi T, Mio F, Miyake A, Miyamoto T, Ozaki K, Takahashi A, Mizuta H, Kubo T, Kimura T, Tanaka T, Toyama Y, Ikegawa S. A functional polymorphism in THBS2 that affects alternative splicing and MMP binding is associated with lumbar-disc herniation. Am J Hum Genet. 2008 May;82(5):1122-9. Epub 2008 May 1. PMID:18455130 doi:S0002-9297(08)00223-1
↑ Tschesche H, Knauper V, Kramer S, Michaelis J, Oberhoff R, Reinke H. Latent collagenase and gelatinase from human neutrophils and their activation. Matrix Suppl. 1992;1:245-55. PMID:1480034
↑ Nuti E, Cuffaro D, D'Andrea F, Rosalia L, Tepshi L, Fabbi M, Carbotti G, Ferrini S, Santamaria S, Camodeca C, Ciccone L, Orlandini E, Nencetti S, Stura EA, Dive V, Rossello A. Sugar-Based Arylsulfonamide Carboxylates as Selective and Water-Soluble Matrix Metalloproteinase-12 Inhibitors. ChemMedChem. 2016 Jun 30. doi: 10.1002/cmdc.201600235. PMID:27356908 doi:http://dx.doi.org/10.1002/cmdc.201600235

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5i12"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the catalytic domain of MMP-9 in complex with a selective sugar-conjugated arylsulfonamide carboxylate water-soluble inhibitor (DC27).==
-<StructureSection load='5i12' size='340' side='right' caption='[[5i12]], [[Resolution|resolution]] 1.59&Aring;' scene=''>
+<StructureSection load='5i12' size='340' side='right'caption='[[5i12]], [[Resolution|resolution]] 1.59&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5i12]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I12 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5I12 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5i12]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I12 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5I12 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=H27:(2R)-2-[{(E)-2-[({(2R,3R,4R,5S,6R)-3-(ACETYLAMINO)-4,5-BIS(ACETYLOXY)-6-[(ACETYLOXY)METHYL]TETRAHYDRO-2H-PYRAN-2-YL}CARBAMOTHIOYL)AMINO]ETHENYL}(BIPHENYL-4-YLSULFONYL)AMINO]-3-METHYLBUTANOIC+ACID'>H27</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=H27:(2R)-2-[{(E)-2-[({(2R,3R,4R,5S,6R)-3-(ACETYLAMINO)-4,5-BIS(ACETYLOXY)-6-[(ACETYLOXY)METHYL]TETRAHYDRO-2H-PYRAN-2-YL}CARBAMOTHIOYL)AMINO]ETHENYL}(BIPHENYL-4-YLSULFONYL)AMINO]-3-METHYLBUTANOIC+ACID'>H27</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5iol|5iol]], [[4hma|4hma]]</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=5i12 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i12 OCA], [http://pdbe.org/5i12 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i12 RCSB], [http://www.ebi.ac.uk/pdbsum/5i12 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5i12 ProSAT]</span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MMP9, CLG4B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5i12 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i12 OCA], [http://pdbe.org/5i12 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i12 RCSB], [http://www.ebi.ac.uk/pdbsum/5i12 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5i12 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 21: / Line 22: @@
 </div>
 <div class="pdbe-citations 5i12" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Matrix metalloproteinase 3D structures|Matrix metalloproteinase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Ciccone, L]]
 [[Category: Cuffaro, D]]

5i12

From Proteopedia

Revision as of 08:40, 27 May 2020

Crystal structure of the catalytic domain of MMP-9 in complex with a selective sugar-conjugated arylsulfonamide carboxylate water-soluble inhibitor (DC27).

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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