Proteinase inhibitors

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).

10p system191 01-06-2013 41 4   Download

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.

7p research12 23-04-2013 37 2   Download

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 di€erent speci®cities towards target proteinases, where SGCI is a good chymo-trypsin inhibitor, itsmutant is apotent trypsin inhibitor, and SGTI inhibits both proteinases weakly.

11p research12 23-04-2013 33 2   Download

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 fromHelicoverpa. ...

10p tumor12 20-04-2013 26 3   Download

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.

8p fptmusic 16-04-2013 28 2   Download

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 unclear.

9p awards 05-04-2013 38 5   Download

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 expressedinthePichiapastorisyeast expressionsystem.

9p dell39 03-04-2013 39 4   Download

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.

11p dell39 27-03-2013 43 3   Download

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.

13p dell39 27-03-2013 43 4   Download

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.

10p galaxyss3 19-03-2013 32 3   Download

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.

13p media19 06-03-2013 42 4   Download

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.

13p viettel02 19-02-2013 34 4   Download

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.

8p tuanloc_muido 11-12-2012 43 5   Download

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)....

13p toshiba23 18-11-2011 67 3   Download

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...

6p toshiba13 22-10-2011 43 3   Download

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...

15p toshiba12 21-10-2011 43 4   Download