5l7f

Crystal structure of MMP12 mutant K421A in complex with RXP470.1 conjugated with fluorophore Cy5,5 in space group P21.Crystal structure of MMP12 mutant K421A in complex with RXP470.1 conjugated with fluorophore Cy5,5 in space group P21.

Structural highlights 5l7f is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , , , , , , , Related: 5czm, 4gql, 5l79 Activity: Macrophage elastase, with EC number 3.4.24.65 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 In designing new tracers consisting of a small-peptide conjugated to a reporter of comparable size, particular attention needs to be paid to the selection of the reporter group which can dictate both the in vitro and in vivo performances of the whole conjugate. In the case of fluorescent tracers, this is particularly true given the large numbers of available dye moieties differing in their structures and properties. Here, we have investigated the in vitro and in vivo properties of a novel series of MMP-12 selective probes composed of cyanine dyes varying in their structure, net charge and hydrophilic character, tethered through a linker to a potent and specific MMP-12 phosphinic pseudo peptide inhibitor. The impact of linker length has been also explored. The crystallographic structure of one tracer in complex with MMP-12 has been obtained, providing the first crystal structure of a Cy5.5-derived probe and confirming that the binding of the targeting moiety is unaffected. MMP-12 remains the tracers privileged target as attested by their affinity selectivity profile evaluated in solution towards a panel of twelve metalloproteases. In vivo assessment of four selected probes has highlighted the impact of the dye structure, but also that of the linker length on the probes blood clearance rates and their biodistributions. These experiments have also provided valuable data on the stability of the dyes moieties in vivo. This has permitted the identification of one probe, which combines favorable binding to MMP-12 in solution and on cells with optimized in vivo performance including blood clearance rate suitable for short-time imaging. Through this series of tracers, we have identified various critical factors modulating the tracers' in vivo behavior, both useful for the development and optimization of MMP-12 selective radiolabeled tracers and informative for the design of fluorescent probes in general. Synthesis, in vitro and in vivo evaluation of MMP-12 selective optical probes.,Bordenave T, Helle M, Beau F, Georgiadis D, Tepshi L, Bernes M, Yunpeng Y, Levenez L, Poquet E, Nozach H, Razavian M, Toczek J, Stura EA, Dive V, Sadeghi MM, Devel L Bioconjug Chem. 2016 Aug 26. PMID:27564088 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 5l7f, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image