Proteinase inhibitors (PIs) are widely distributed in plants, microorganisms and
mammalian species; they are known to play pivotal roles in regulating proteinase activities in these
species. Accordingly, PIs are important molecular tools for many research disciplines. Studies of
the correlation of PI structures and functions have lead to understanding of their inhibitory actions
against physiological important proteases. There are potential therapeutic applications for such
studies for diseases relating to excessive activities of proteases.
Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học 'Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: "Neutrophil elastase reduces secretion of secretory leukoproteinase inhibitor (SLPI) by lung epithelial cells: role of charge of the proteinase-inhibitor complex...
The interaction of proteinase inhibitors produced, in most cases, by host
organisms and the invasive proteinases of pathogens or parasites or the
dietary proteinases of predators, results in an evolutionary ‘arms race’ of
rapid and ongoing change in both interacting proteins.
Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học 'Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: The role of secretory leukocyte proteinase inhibitor and elafin (elastase-specific inhibitor/skin-derived antileukoprotease) as alarm antiproteinases in inflammatory lung disease...
Yeast IA3 aspartic proteinase inhibitor operates through an unprecedented
mechanism and exhibits a remarkable specificity for one target enzyme, sac-charopepsin. Even aspartic proteinases that are very closely similar to
saccharopepsin (e.g. the vacuolar enzyme fromPichia pastoris) are not sus-ceptible to significant inhibition.
The solution structure of three small serine proteinase
inhibitors, two natural and one engineered protein,
SGCI (Schistocerca gregaria chymotrypsin inhibitor),
SGCI[L30R, K31M] and SGTI (Schistocerca gregaria
trypsin inhibitor), were determined by homonuclear NMR-spectroscopy. The molecules exhibit dierent speci®cities
towards target proteinases, where SGCI is a good chymo-trypsin inhibitor, itsmutant is apotent trypsin inhibitor, and
SGTI inhibits both proteinases weakly.
Plasminogen activator inhibitor-1 (PAI-1) belongs to the
serpin family of serine proteinase inhibitors. Serpins inhibit
their target proteinases by an ester bond being formed
between the active site serine of the proteinase and the P1
residue of the reactive centre loop (RCL) of the serpin, fol-lowed by insertion of the RCL intob-sheet A of the serpin.
Concomitantly, there are conformational changes in the
flexible joint region lateral tob-sheet A.
Pest insects such asHelicoverpaspp. frequently feed on
plants expressing protease inhibitors. Apparently, their
digestive system can adapt to the presence of protease
inhibitors. To study this, a trypsin enzymewas purified from
the gut of insects that were raised on an inhibitor-containing
diet. The amino-acid sequence of this enzyme was analysed
by tandem MS, which allowed assignment of 66% of the
mature protein amino acid sequence. This trypsin, called
HzTrypsin-S, corresponded to a known cDNA sequence
Medicinal chemistry is a discipline at the intersection of chemistry, especially synthetic
organic chemistry, and pharmacology and various other biological specialties, where
they are involved with design, chemical synthesis and development for market of
pharmaceutical agents (drugs). Compounds used in medical applications are most
often organic compounds, which are often divided into the broad classes of small
organic molecules and biologics, the latter of which are most often medicinal
preparations of proteins. Inorganic and organometallic compounds are also useful as
Abstract Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases that are capable of cleaving all extra cellular matrix (ECM) substrates. Degradation of matrix is a key event in progression, invasion and metastasis of potentially malignant and malignant lesions of the head and neck. It might have an important polymorphic association at the promoter regions of several MMPs such as MMP-1 (-1607 1G/2G), MMP-2 (-1306 C/T), MMP-3 (-1171 5A/6A), MMP-9 (-1562 C/T) and TIMP-2 (-418 G/C or C/C)....
Trappin-2 (also known as pre-elafin) is an endogenous inhibitor of neutro-phil serine proteases and is involved in the control of excess proteolysis,
especially in inflammatory events, along with the structurally related secre-tory leucocyte proteinase inhibitor.
Neutrophil proteinase-mediated lung tissue destruction is prevented by
inhibitors, including elafin and its precursor, trappin. We wanted to estab-lish whether neutrophil-derived oxidants might impair the inhibitory func-tion of these molecules. Myeloperoxidase⁄H2O2 and N-chlorosuccinimide
oxidation of the inhibitors was checked by mass spectrometry and enzy-matic methods.
Elafin and its precursor, trappin-2 or pre-elafin, are specific
endogenous inhibitors of human neutrophil elastase and
proteinase 3 but not of cathepsin G. Both inhibitors belong,
together with secretory leukocyte protease inhibitor, to the
chelonianin family of canonical protease inhibitors of serine
proteases. AcDNAcoding either elafin or its precursor,
trappin-2, was fused in framewith yeasta-factor cDNAand
The serpins are of general protein chemical interest due to their ability to undergo a large conformational change consisting of the insertion of the reactive centre loop (RCL) as strand 4 of the central b sheet A. To make space for the incoming RCL, the ‘shutter region’ opens by the b strands 3A and 5A sliding apart over the underlying a helix B. Loop insertion occurs during the formation of complexes of serpins with their target serine proteinases and during latency transition. This type of loop insertion is unique to plasminogen activator inhibitor-1 (PAI-1).
A cDNA library from tobacco inoculated withRhizoctonia solaniwas con-structed, and several cDNA fragments were identified by differential
hybridization screening. One cDNA clone that was dramatically repressed,
NtKTI1, was confirmed as a member of the Kunitz plant proteinase inhibi-tor family. RT-PCR analysis revealed that NtKTI1was constitutively
expressed throughout the whole plant and preferentially expressed in the
roots and stems.
The crystal structure of a heparin cofactor II (HCII)–
thrombin Michaelis complex has revealed extensive con-tacts encompassing the N-terminal domain of HCII and
exosite I of the proteinase. In contrast, the location of the
N-terminal extension in the uncomplexed inhibitor was
Proteinases are involved in different crucial living processes such as digestion,
germination, growth, development, metamorphism, fertilisation, blood clotting, infection
diseases, cancer etc. Therefore their protein inhibitors (PPIs) – an effective regulation
factors have been used in medicine for treatment of diseases and in agriculture to improve
plant resistance to pest insects.
The HIV-1 proteinase (PR) has proved to be a good target
for antiretroviral therapy of AIDS, and various PR inhibi-tors are now in clinical use. However, there is a rapid selec-tionof viral variantsbearingmutations in theproteinase that
are resistant to clinical inhibitors. Drug resistance also
involves mutations of the nucleocapsid/p1 and p1/p6 clea-vage sites ofGag, bothin vitroandin vivo.