title: Human placental extract mediated inhibition of proteinase K: implications of heparin and glycoproteins in wound physiology.
abstract: Efficient debridement of the wound bed following the removal of microbial load prevents its progression into a chronic wound. Bacterial infection and excessive proteolysis characterize impaired healing and therefore, their inhibition might restore the disturbed equilibrium in the healing process. Human placental extract exhibits reversible, non-competitive inhibition towards Proteinase K, a microbial protease, by stabilizing it against auto-digestion. Scattering and fluorescence studies followed by biochemical analysis indicated the involvement of a glycan moiety. Surface plasmon resonance demonstrated specific interaction of heparin with Proteinase K having Kd in μM range. Further, Proteinase K contains sequence motifs similar to other heparin-binding proteins. Molecular docking revealed presence of clefts suitable for binding of heparin-derived oligosaccharides. Comprehensive analysis of this inhibitory property of placental extract partly explains its efficacy in curing wounds with common bacterial infections.
authors.affiliation: Division of Structural Biology and﻿ Bioinformatics, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata, India.
authors.forename: Kanika
authors.initials: K
authors.lastname: Sharma
authors.forename: Chaitali
authors.initials: C
authors.lastname: Mukherjee
authors.forename: Siddhartha
authors.initials: S
authors.lastname: Roy
authors.forename: Debashree
authors.initials: D
authors.lastname: De
authors.forename: Debasish
authors.initials: D
authors.lastname: Bhattacharyya
mesh_terms: D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D019286:Endopeptidase K / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D004795:Enzyme Stability; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006493:Heparin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D010924:Placental Extracts / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence; D020349:Surface Plasmon Resonance; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D006023:Glycoproteins; D010924:Placental Extracts; D015842:Serine Proteinase Inhibitors; D006493:Heparin; D019286:Endopeptidase K