5i4o

From Proteopedia

Crystal structure of the catalytic domain of MMP-12 in complex with a selective sugar-conjugated triazole-linked carboxylate zinc-chelator water-soluble inhibitor (DC28).

Structural highlights

5i4o is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.05Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MMP12_HUMAN May be involved in tissue injury and remodeling. Has significant elastolytic activity. Can accept large and small amino acids at the P1' site, but has a preference for leucine. Aromatic or hydrophobic residues are preferred at the P1 site, with small hydrophobic residues (preferably alanine) occupying P3.

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^[1]

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

References

↑ 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 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://proteopedia.org/wiki/index.php/5i4o"

5i4o

From Proteopedia

Crystal structure of the catalytic domain of MMP-12 in complex with a selective sugar-conjugated triazole-linked carboxylate zinc-chelator water-soluble inhibitor (DC28).

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox