title: The 15-domain serine proteinase inhibitor LEKTI: biochemical properties, genomic organization, and pathophysiological role.
abstract: Proteinases are involved in specific and non-specific proteolytic reactions, and participate in many pathophysiological processes. Normally, they are regulated by endogenously produced proteinase inhibitors which, thus, represent lead structures for the development of therapeutics. We succeeded in partially isolating and cloning a novel human serine proteinase inhibitor which, according to its structure and the expression pattern of the corresponding gene, was termed lympho-epithelial Kazal-type-related inhibitor (LEKTI). This inhibitor is of special interest because it exhibits an extraordinarily large number of 15 potentially inhibitory domains and is of pathophysiological importance for the severe congenital disease Netherton syndrome. Here, we review the as yet known data on protein structure, biochemical properties, genomic organization and gene expression. Furthermore, the relevance of LEKTI for several disorders pointing out its possible future therapeutic value, is discussed.
authors.affiliation: IPF PharmaCeuticals GmbH, An-Institut der Medizinischen Hochschule Hannover, Feodor-Lynen-Str. 31, D-30625 Hannover, Germany. HJ-Maegert@gmx.de
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Mägert
authors.forename: P
authors.initials: P
authors.lastname: Kreutzmann
authors.forename: K
authors.initials: K
authors.lastname: Drögemüller
authors.forename: L
authors.initials: L
authors.lastname: Ständker
authors.forename: K
authors.initials: K
authors.lastname: Adermann
authors.forename: M
authors.initials: M
authors.lastname: Walden
authors.forename: H
authors.initials: H
authors.lastname: John
authors.forename: H C
authors.initials: HC
authors.lastname: Korting
authors.forename: W G
authors.initials: WG
authors.lastname: Forssmann
mesh_terms: D000818:Animals; D002352:Carrier Proteins; D015870:Gene Expression; D006801:Humans; D016113:Ichthyosiform Erythroderma, Congenital / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary / Q000502:physiology; D053491:Proteinase Inhibitory Proteins, Secretory; D017386:Sequence Homology, Amino Acid; D000074163:Serine Peptidase Inhibitor Kazal-Type 5; D015842:Serine Proteinase Inhibitors / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology*; D013577:Syndrome
chemical_list: D002352:Carrier Proteins; D053491:Proteinase Inhibitory Proteins, Secretory; C120650:SPINK5 protein, human; D000074163:Serine Peptidase Inhibitor Kazal-Type 5; D015842:Serine Proteinase Inhibitors