3vfe

Virtual Screening and X-Ray Crystallography for Human Kallikrein 6 Inhibitors with an Amidinothiophene P1 GroupVirtual Screening and X-Ray Crystallography for Human Kallikrein 6 Inhibitors with an Amidinothiophene P1 Group

Structural highlights 3vfe is a 1 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 1.88Å Ligands: Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function KLK6_HUMAN Serine protease which exhibits a preference for Arg over Lys in the substrate P1 position and for Ser or Pro in the P2 position. Shows activity against amyloid precursor protein, myelin basic protein, gelatin, casein and extracellular matrix proteins such as fibronectin, laminin, vitronectin and collagen. Degrades alpha-synuclein and prevents its polymerization, indicating that it may be involved in the pathogenesis of Parkinson disease and other synucleinopathies. May be involved in regulation of axon outgrowth following spinal cord injury. Tumor cells treated with a neutralizing KLK6 antibody migrate less than control cells, suggesting a role in invasion and metastasis. Publication Abstract from PubMed A series of compounds with an amidinothiophene P1 group and a pyrrolidinone-sulphonamide scaffold linker was identified as potent inhibitors of human kallikrein 6 by structure-based virtual screening based on the union accessible binding space of serine proteases. As the first series of potent nonmechanism-based hK6 inhibitors, they may be used as tool compounds for target validation. An X-ray structure of a representative compound complexed with hK6, resolved at a resolution of 1.88 A, revealed that the amidinothiophene moiety bound in the S1 pocket and the pyrrolidinone-sulphonamide linker projected the aromatic tail into the S' pocket. Virtual Screening and X-ray Crystallography for Human Kallikrein 6 Inhibitors with an Amidinothiophene P1 Group.,Liang G, Chen X, Aldous S, Pu SF, Mehdi S, Powers E, Giovanni A, Kongsamut S, Xia T, Zhang Y, Wang R, Gao Z, Merriman G, McLean LR, Morize I ACS Med Chem Lett. 2012 Jan 11;3(2):159-64. doi: 10.1021/ml200291e. eCollection , 2012 Feb 9. PMID:24900446 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Kallikrein 3D structures

spinqualitylabelsall models 3vfe, resolution 1.88Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image