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1 albumin serine protease inhibitor family (ov-serpin).
2 conformation would lead to inactive, latent serpin.
3 n to modulate the inhibitory function of the serpin.
4 se proteins endochitinase A, PR-4, PRms, and SerPIN.
5 determines the inhibitory selectivity of the serpin.
6 determining the protease specificity of the serpin.
7 al binding of selected DHP structures to the serpin.
8 affinity was seen between native and cleaved serpin.
9 reactive site recognition determinants in a serpin.
10 induce full conformational activation of the serpin.
11 -approved small molecule inactivators of any serpins.
12 oteases can be regulated after activation by serpins.
13 he susceptibility of fibrinolytic enzymes to serpins.
14 s for all tested natural thrombin-inhibiting serpins.
15 rine proteases and their specific inhibitors serpins.
16 and is different from other heparin-binding serpins.
17 arge protein substrates and inhibitors, like serpins.
18 tial to extend immunomodulatory functions of serpins.
19 those of well studied human and prokaryotic serpins.
24 lasma we used immunoaffinity purification of serpin-1 isoforms from M. sexta plasma, followed by two-
25 rnative splicing produces transcripts for 12 serpin-1 isoforms in Manduca sexta that differ only in t
26 To investigate the presence of individual serpin-1 isoforms in plasma we used immunoaffinity purif
27 dgut chymotrypsin was identified, suggesting serpin-1 isoforms may also function to protect insect ti
28 melanization proteases (IMP-1 and IMP-2) and Serpin-1 mediate hemolymph prophenoloxidase cleavage and
29 1 isoforms and, through analysis of putative serpin-1-proteinase complexes, identified three endogeno
34 ents, there were higher levels of unmodified serpin A1 and A3, but following treatments with redox ac
35 spectrometry analyses identified Cys(256) of serpin A1 and Cys(263) of serpin A3 as the S-glutathiony
36 There is potential for S-glutathionylated serpins A1 and A3 to act as pharmacodynamic biomarkers f
37 es and mass spectrometry, we identified that serpins A1 and A3 were S-glutathionylated in a dose- and
38 eral adipose tissue-derived serpin (vaspin), serpin A12 of the serpin family, and its target protease
40 r results constitute an in vivo example of a Serpin acting as a suicide inhibitor in plants, reminisc
41 sampling algorithm, we simulated the entire serpin active-to-latent transition in all-atom detail wi
42 evealed an association between baseline anti-serpin activity and slower residual beta cell function d
43 istent with the hypothesis that anti-clade B serpin activity blocks the serpin from binding, exposure
45 correction restores Z-alpha1AT secretion and serpin activity to a level 50% that observed for wild-ty
47 orresponding loop of the non-heparin-binding serpin alpha(1)-proteinase inhibitor (ZPI-D-helix(alpha1
48 g the ability of component peptides from the serpin alpha(1)PI to associate, we have now elucidated t
51 n the active-to-latent transition of another serpin, alpha1-antitrypsin, which does not readily go la
52 cific fluorophore-labeled derivatives of the serpin, alpha1-protease inhibitor (alpha1PI), which repo
53 Compared with other Ser protease inhibitors (serpins), alpha2AP contains an ~50-residue-extended C-te
56 provide new insights into the nature of the serpin and protease conformational changes involved in t
57 tease inhibitor (alpha1PI), which report the serpin and protease conformational changes involved in t
62 mation of thrombin in its final complex with serpins and find that in addition to exosite I, exosite
64 m can be successfully targeted by engineered serpins and that administration of such agents is effect
65 s, from plants to vertebrates, now show that serpins and their unique inhibitory mechanism and confor
66 tiproteases, including leupeptin, aprotinin, serpins, and alpha2-macroglobulin, suggesting the presen
67 Thus, miropin is unique among inhibitory serpins, and it has apparently evolved the ability to in
70 own that residues Tyr-253 and Glu-255 in the serpin antithrombin function as exosites to promote the
72 rates inhibition of factor XIa (fXIa) by the serpins antithrombin (AT) and C1-inhibitor (C1-INH) by m
73 ycosaminoglycans allosterically activate the serpin, antithrombin, by binding through a specific pent
74 n allosteric activation of the anticoagulant serpin, antithrombin, is the release of the reactive cen
77 tion, an increasing number of non-inhibitory serpins are emerging as important elements within a dive
79 ences in expression pattern suggest that the serpins are involved in multiple physiological processes
85 ccount for the effect of heparin with either serpin, as the second-order inhibition rate constants di
86 ice with a monoclonal antibody (mAb) against serpin B13 also leads to fewer inflammatory cells in the
89 enous anti-serpin B13 mAb or endogenous anti-serpin B13 autoantibodies resulted in cleavage of the su
90 conclude that anti-serpin antibodies prevent serpin B13 from neutralizing proteases, thereby impairin
93 pin from binding, exposure to exogenous anti-serpin B13 mAb or endogenous anti-serpin B13 autoantibod
94 hy young Balb/c male mice were injected with serpin B13 mAb or IgG control and examined for the numbe
96 n B13 mAb blocked the inhibitory activity of serpin B13, thereby allowing partial preservation of the
97 so documented the perivascular expression of Serpin B2 by angiotropic melanoma cells in the murine br
98 f anti-PA serpins, including neuroserpin and serpin B2, to prevent plasmin generation and its metasta
99 annexin V, heparanase, ERp57, kallekrein-14, serpin B6, tetranectin, and collagen VI showed a bias fo
100 ifferentially affected furin reactivity with serpin B8 and alpha1PDX in a manner that depended on the
101 inhibitor of furin, together with alpha1PDX-serpin B8 and furin-PC chimeras to identify determinants
102 p (RCL) sequences of alpha1PDX with those of serpin B8 demonstrated that both the P4-P1 RXXR recognit
103 te loops whose role in furin reactivity with serpin B8 was tested by engineering furin-PC loop chimer
107 n, chloride channel accessory 1 (CLCA1), and Serpin beta2 (SERPINB2) in airway epithelial brushings i
108 phan fluorescence suggested a common mode of serpin binding, involving lysines on the serpin engaging
109 ntermediate trapping mechanism used by other serpins, but with significant variations of this mechani
110 htly regulated in healthy individuals by the serpin C1-inhibitor, but individuals with hereditary ang
112 f action, these SPIs can be categorized into serpins, canonical inhibitors and alpha-2-macroglobulins
113 unexpected EPO action mode via an EPOR-Spi2A serpin-cathepsin axis in maturing erythroblasts, with ly
114 placentation: the prolactins (two clusters), serpins, cathepsins, and the natural killer (NK)/C-type
116 levels of fXII, and reduced levels of fXIIa-serpin complexes, consistent with fXII being a substrate
120 r inhibition of proteinases, so that massive serpin conformational change, driven by the favorable en
121 through a unique mechanism in which a major serpin conformational change, resulting in a 70-A transl
122 ion and movement of the protease and coupled serpin conformational changes involving the F helix-shee
125 t the crystallographic structure of a stable serpin dimer which reveals a domain swap of more than 50
127 ude a unique profile of cytokines, including Serpin E1, which is not generated by other T cells, MIF,
128 the exquisite specificity that makes a given serpin effective only when certain other criteria, such
129 ave now elucidated the pathway by which this serpin efficiently folds into its metastable state.
130 of serpin binding, involving lysines on the serpin engaging the acidic region around the calcium bin
131 e presence of proteinase in complex with the serpin enhanced affinity modestly and presumably nonspec
134 serpin B8-furin Michaelis complex identified serpin exosites in strand 3C close to the 298-300 loop w
136 nant human PEDF (rhuPEDF) was cleaved at its serpin-exposed loop by limited chymotrypsin proteolysis.
137 ions also help elucidate why some inhibitory serpin families are more conformationally labile than ot
138 tichymotrypsin (alpha1-ACT), a member of the serpin family (SERPINA3), is an acute-phase protein secr
139 a nonsynonymous single-nucleotide variant in serpin family A member 1 (SERPINA1) encoding alpha-1 ant
140 ibitor Portland (alpha1PDX) is an engineered serpin family inhibitor of the proprotein convertase (PC
144 a antigens 1 and 2 (SCCA1/2), members of the Serpin family of serine/cysteine protease inhibitors, ar
146 e-derived serpin (vaspin), serpin A12 of the serpin family, and its target protease kallikrein 7 (KLK
148 e other thrombin inhibitors belonging to the serpin family, PN1 is not synthesized in the liver and d
151 ogenous inhibitors of APC are members of the serpin family: protein C inhibitor (PCI) and alpha1-anti
152 ny members of the serine protease inhibitor (serpin) family are activated by glycosaminoglycans (GAGs
153 ectin 1 (FN1) and serine protease inhibitor (serpin) family E member 2 (SERPINE2) are essential for V
154 s a member of the serine protease inhibitor (serpin) family of proteins, whose target proteases inclu
156 een shown that the formation of the thrombin-serpin final complex disorders the active site and exosi
157 ever, conformational labiality of the native serpin fold renders them susceptible to misfolding, whic
162 that anti-clade B serpin activity blocks the serpin from binding, exposure to exogenous anti-serpin B
164 phylogenetic clusters with known inhibitory serpins from Drosophila melanogaster and Manduca sexta.
165 s for potent and selective modulation of the serpin function, especially for inhibiting the initiatio
166 suggest a novel framework for understanding serpin function, especially with respect to thrombin inh
167 y with respect to thrombin inhibition, where serpins functionally "rezymogenize" proteases to ensure
171 icroorganisms, and only very few prokaryotic serpins have been investigated from a mechanistic standp
172 posure to proteases within the cell, clade B serpins help to maintain homeostasis by inducing protect
174 le inactivation of alpha-thrombin (T) by the serpin, heparin cofactor II (HCII), is accelerated by te
176 All prokaryotic genes encoding putative serpins identified to date are found in environmental an
177 Our findings reveal a new role for the anti-serpin immunological response in promoting adaptive chan
179 ering, indicating a functional role for this SERPIN in the dual-growth factor model of induced motili
180 n, and plasminogen activator (PA) inhibitory serpins in cancer cells as a shield against this defense
181 est that elevated circulating antiangiogenic serpins in diabetic patients may contribute to impaired
182 minireview examines use of exosites by nine serpins in the initial complex-forming phase to modulate
183 pe 1 (PAI-1) is a serine protease inhibitor (serpin) in which the reactive center loop (RCL) spontane
184 breast cancer express high levels of anti-PA serpins, including neuroserpin and serpin B2, to prevent
188 asminogen activator inhibitor 1 (PAI-1) is a serpin inhibitor of the plasminogen activators urokinase
189 inhibitor (ZPI) are among two physiological serpin inhibitors in plasma that are involved in the reg
193 lts support a model in which linkage between serpins is achieved through insertion of the reactive ce
194 ted acceleration of fXIa inhibition by these serpins is incompletely understood, as heparin appears t
196 oop docking site to the opposite pole of the serpin, kinetically traps the acyl-intermediate complex.
197 ovel EPO-triggered pathway involving a Spi2A serpin-lysosome-cathepsin cascade that is initiated thro
206 miniscent of the activity of animal or viral serpins on immune/cell death regulators, including caspa
207 c colonization, suggesting that mutations in serpins or other members of the coagulation cascade can
209 ks centred on apolipoprotein E, jun, leptin, serpin peptidase inhibitor E type 1 and peroxisome proli
210 and potentially interdependent induction of serpin peptidase inhibitor, clade A member 3 (SERPINA3)
213 ltiple mutations were found in the SERPINF1 (Serpin Peptidase Inhibitor, Clade F) gene which encodes
214 n-like-8 (MTRNRL8), interleukin-8 (IL8), and serpin peptidase inhibitor, clade H (SERPINH1) and chemo
220 strated that plasminogen activator inhibitor serpins promote brain metastatic colonization, suggestin
221 ously identified KCs as a rich source of the serpin protease inhibitor vaspin (serpinA12), originally
223 sed on a proteomic screen, we identified the serpin protease nexin-1 (PN-1) as a potential target of
225 in trapping the acyl-intermediate complex in serpin-protease reactions and support a previously propo
229 actor (PEDF) is a serine protease inhibitor (serpin) protein with well established neuroprotective an
231 odulate primary specificity in either binary serpin-proteinase complexes or ternary complexes that ad
233 ls and fostering vascular co-option, anti-PA serpins provide a unifying mechanism for the initiation
236 observed in the reactions, ascribable to (i) serpin reactive center loop insertion into sheet A with
238 n(298-300) loop are critical determinants of serpin reactivity with furin, which may be exploited in
241 proteases cleaving the bait they offer (e.g. serpins, regulating cell death, and alpha-macroglobulins
243 m and may be an important determinant of the serpin's protection against developing cigarette smoke-i
248 active center loop residues of the prototype serpin, SERPINA1, with the P4-P5' residues of Sb9 contai
249 oci at genome-wide significance, the clade B serpin (SERPINB) gene cluster at 18q21.3, the cytokine g
250 nt and phylogenetic tree indicated that some serpins similar to known functional inhibitory serpins m
251 urin-PC chimeras to identify determinants of serpin specificity and selectivity for furin inhibition.
254 of these autoantigens are homologues of the serpin, squamous cell carcinoma antigen (SCCA), the othe
257 enome provides an opportunity to investigate serpin structure, function, and evolution at the genome
260 clinically relevant role for a member of the serpin superfamily and a leukocyte elastase and crosstal
261 (ZPI) is a recently identified member of the serpin superfamily that functions as a cofactor-dependen
263 s a member of the serine protease inhibitor (serpin) superfamily and displays tumor-suppressing activ
264 se members of the serine protease inhibitor (serpin) superfamily to undergo a novel conformational tr
265 a member of the serine proteinase inhibitor (SERPIN) superfamily with antiangiogenic activities, were
266 nsus design to create conserpin, a synthetic serpin that folds reversibly, is functional, thermostabl
268 r human or mouse Sb9 results in a functional serpin that inhibits GzmB and resists ROS inactivation.
271 ently identified a novel antibody to clade B serpin that reduces islet-associated T cell accumulation
272 tease inhibitor 9 (PI-9) is an intracellular serpin that specifically inhibits granzyme B, a cytotoxi
274 a non-inhibitory serine protease inhibitor (serpin) that influences many cellular functions includin
277 igh affinity (K(D) = 30nM) and activated the serpin to rapidly (k(ass) approximately 10(6)M(-1)s(-1))
278 G has adapted an allosteric mechanism of the serpins to allow equilibrated release of the hormones by
279 leted sequencing of cDNAs for the A. gambiae serpins to obtain complete coding sequence information a
280 avage, CBG undergoes the irreversible S-to-R serpin transition, with the cleaved reactive loops being
287 drugs, relative S-glutathionylation of these serpins was higher in plasma from normal individuals.
288 between uncomplexed and proteinase-complexed serpins, we have systematically examined the affinities
289 cting the allosteric activation state of the serpin were inconsistent with a two-state model of allos
291 physiological inhibitors of thrombin are all serpins, whose mechanism involves significant conformati
292 ing the biological functions of the mosquito serpins will require future work to identify the proteas
294 m-derived factor (PEDF) is a multifunctional serpin with antitumorigenic, antimetastatic, and differe
296 tes the exosite-dependent interaction of the serpin with factors IXa (FIXa) and Xa (FXa), thereby imp
297 ome the repulsive inhibitory interactions of serpins with basic residues on the fXIa 148 and 37 loops
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