4k8y | pdb_00004k8y

Atomic resolution crystal structures of Kallikrein-Related Peptidase 4 complexed with Sunflower Trypsin Inhibitor (SFTI-1)

spinqualitylabelsall models 4k8y, resolution 1.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4k8y is a 2 chain structure with sequence from Helianthus annuus and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1Å Ligands: PRD_001097 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease KLK4_HUMAN Defects in KLK4 are the cause of amelogenesis imperfecta hypomaturation type 2A1 (AI2A1) [MIM:204700. AI2A1 is an autosomal recessive defect of enamel formation. The disorder involves both primary and secondary dentitions. The teeth have a shiny agar jelly appearance and the enamel is softer than normal. Brown pigment is present in middle layers of enamel. Function KLK4_HUMAN Involved in enamel formation. Publication Abstract from PubMed The kallikrein-related peptidase (KLK) family of proteases is involved in many aspects of human health and disease. One member of this family, KLK4, has been implicated in cancer development and metastasis. Understanding mechanisms of inactivation are critical to developing selective KLK4 inhibitors. We have determined the X-ray crystal structures of KLK4 in complex with both sunflower trypsin inhibitor-1 (SFTI-1) and a rationally designed SFTI-1 derivative to atomic (~1 A) resolution, as well as with bound nickel. These structures offer a structural rationalization for the potency and selectivity of these inhibitors, and together with MD simulation and computational analysis, reveal a dynamic pathway between the metal binding exosite and the active site, providing key details of a previously proposed allosteric mode of inhibition. Collectively, this work provides insight into both direct and indirect mechanisms of inhibition for KLK4 that have broad implications for the enzymology of the serine protease superfamily, and may potentially be exploited for the design of therapeutic inhibitors. Direct and indirect mechanisms of KLK4 inhibition revealed by structure and dynamics.,Riley BT, Ilyichova O, Costa MG, Porebski BT, de Veer SJ, Swedberg JE, Kass I, Harris JM, Hoke DE, Buckle AM Sci Rep. 2016 Oct 21;6:35385. doi: 10.1038/srep35385. PMID:27767076 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Kallikrein 3D structures Trypsin inhibitor 3D structures

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