Related ArticlesNMR and bioinformatics discovery of exosites that tune metalloelastase specificity for solubilized elastin and collagen triple helices.
J Biol Chem. 2010 Oct 1;285(40):30918-30
Authors: Palmier MO, Fulcher YG, Bhaskaran R, Duong VQ, Fields GB, Van Doren SR
The catalytic domain of metalloelastase (matrix metalloproteinase-12 or MMP-12) is unique among MMPs in exerting high proteolytic activity upon fibrils that resist hydrolysis, especially elastin from lungs afflicted with chronic obstructive pulmonary disease or arteries with aneurysms. How does the MMP-12 catalytic domain achieve this specificity? NMR interface mapping suggests that ?-elastin species cover the primed subsites, a strip across the ?-sheet from ?-strand IV to the II-III loop, and a broad bowl from helix A to helix C. The many contacts may account for the comparatively high affinity, as well as embedding of MMP-12 in damaged elastin fibrils in vivo. We developed a strategy called BINDSIght, for bioinformatics and NMR discovery of specificity of interactions, to evaluate MMP-12 specificity without a structure of a complex. BINDSIght integration of the interface mapping with other ambiguous information from sequences guided choice mutations in binding regions nearer the active site. Single substitutions at each of ten locations impair specific activity toward solubilized elastin. Five of them impair release of peptides from intact elastin fibrils. Eight lesions also impair specific activity toward triple helices from collagen IV or V. Eight sites map to the "primed" side in the III-IV, V-B, and S1' specificity loops. Two map to the "unprimed" side in the IV-V and B-C loops. The ten key residues circumscribe the catalytic cleft, form an exosite, and are distinctive features available for targeting by new diagnostics or therapeutics.
[NMR paper] New carbohydrate specificity and HIV-1 fusion blocking activity of the cyanobacterial
New carbohydrate specificity and HIV-1 fusion blocking activity of the cyanobacterial protein MVL: NMR, ITC and sedimentation equilibrium studies.
Related Articles New carbohydrate specificity and HIV-1 fusion blocking activity of the cyanobacterial protein MVL: NMR, ITC and sedimentation equilibrium studies.
J Mol Biol. 2004 Jun 11;339(4):901-14
Authors: Bewley CA, Cai M, Ray S, Ghirlando R, Yamaguchi M, Muramoto K
Carbohydrate-binding proteins that bind their carbohydrate ligands with high affinity are rare and therefore of interest because...
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[NMR paper] Heteronuclear NMR studies of the specificity of the post-translational modification o
Heteronuclear NMR studies of the specificity of the post-translational modification of biotinyl domains by biotinyl protein ligase.
Related Articles Heteronuclear NMR studies of the specificity of the post-translational modification of biotinyl domains by biotinyl protein ligase.
FEBS Lett. 2000 Aug 18;479(3):93-8
Authors: Reche PA, Howard MJ, Broadhurst RW, Perham RN
The lipoyl domains of 2-oxo acid dehydrogenase multienzyme complexes and the biotinyl domains of biotin-dependent enzymes have homologous structures, but the target lysine...
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[NMR paper] Structural-functional bioinformatics: knowledge-based NMR interpretation.
Structural-functional bioinformatics: knowledge-based NMR interpretation.
Related Articles Structural-functional bioinformatics: knowledge-based NMR interpretation.
Stud Health Technol Inform. 1998;52 Pt 1:365-6
Authors: Kulikowski CA, Zimmerman D, Montelione G, Anderson S
This paper describes a knowledge-based approach to a problem of structural-functional bioinformatics, specifically the determination of protein structure through the automated analysis of NMR data. Highly successful results in carrying out sequence-specific assignments of...
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[NMR paper] 111Cd NMR studies of the domain specificity of Ag+ and Cu+ binding to metallothionein
111Cd NMR studies of the domain specificity of Ag+ and Cu+ binding to metallothionein.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--pubs.acs.org-images-acspubs.jpg Related Articles 111Cd NMR studies of the domain specificity of Ag+ and Cu+ binding to metallothionein.
Biochemistry. 1996 Nov 5;35(44):13929-36
Authors: Li H, Otvos JD
Metal displacement reactions of Cd7MT with Ag+ or Cu+ and interprotein metal exchange reactions between Cd7MT and Ag12MT or Cu12MT were studied by 111Cd NMR. Titration of 111Cd7MT with Ag+ indicates that...
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NMR in Structural Biology - Alessandro Pintar, Protein Structure and Bioinformatics, ICGEB, Trieste
Nuclear Magnetic Resonance in Structural Biology - Alessandro Pintar, Protein Structure and Bioinformatics, ICGEB, Trieste
Thanks to advancements both in the theory and in the instrumentation, Nuclear Magnetic Resonance (NMR) has widened its use from small organic molecules to oligosaccharides, peptides, proteins, and nucleic acids. Together with X-ray crystallography, NMR is the only technique that can provide structural information at the atomic level. However, applications of NMR are not limited to 3D structure calculation: it can be used to study flexible biomolecules (peptides,...