4ayk

CATALYTIC FRAGMENT OF HUMAN FIBROBLAST COLLAGENASE COMPLEXED WITH CGS-27023A, NMR, 30 STRUCTURES

spinqualitylabelsall models 4ayk, 30 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ayk is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CA, CGS, ZN Activity: Interstitial collagenase, with EC number 3.4.24.7 Resources: FirstGlance, OCA, RCSB, PDBsum Function [MMP1_HUMAN] Cleaves collagens of types I, II, and III at one site in the helical domain. Also cleaves collagens of types VII and X. In case of HIV infection, interacts and cleaves the secreted viral Tat protein, leading to a decrease in neuronal Tat's mediated neurotoxicity. 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 The solution structure of the catalytic fragment of human fibroblast collagenase (MMP-1) complexed with a sulfonamide derivative of a hydroxamic acid compound (CGS-27023A) has been determined using two-dimensional and three-dimensional heteronuclear NMR spectroscopy. The solution structure of the complex was calculated by means of hybrid distance geometry-simulated annealing using a combination of experimental NMR restraints obtained from the previous refinement of the inhibitor-free MMP-1 (1) and recent restraints for the MMP-1:CGS-27023A complex. The hydroxamic acid moiety of CGS-27023A was found to chelate to the "right" of the catalytic zinc where the p-methoxyphenyl sits in the S1' active-site pocket, the isopropyl group is in contact with H83 and N80, and the pyridine ring is solvent exposed. The sulfonyl oxygens are in hydrogen-bonding distance to the backbone NHs of L81 and A82. This is similar to the conformation determined by NMR of the inhibitor bound to stromelysin (2, 3). A total of 48 distance restraints were observed between MMP-1 and CGS-27023A from 3D 13C-edited/12C-filtered NOESY and 3D 15N-edited NOESY experiments. An additional 18 intramolecular restraints were observed for CGS-27023A from a 2D 12C-filtered NOESY experiment. A minimal set of NMR experiments in combination with the free MMP-1 assignments were used to assign the MMP-1 (1)H, 13C, and 15N resonances in the MMP-1:CGS-27023A complex. The assignments of CGS-27023A in the complex were obtained from 2D 12C-filtered NOESY and 2D 12C-filtered TOCSY experiments. NMR solution structure of the catalytic fragment of human fibroblast collagenase complexed with a sulfonamide derivative of a hydroxamic acid compound.,Moy FJ, Chanda PK, Chen JM, Cosmi S, Edris W, Skotnicki JS, Wilhelm J, Powers R Biochemistry. 1999 Jun 1;38(22):7085-96. PMID:10353819 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Matrix metalloproteinase

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