ライフサイエンスコーパス: memapsin

1 ve site residues to provide selectivity over memapsin 1 and cathepsin D.

2 uman membrane-associated aspartic proteases, memapsin 1 and memapsin 2, have been cloned and sequence

3 memapsin 2 inhibitors effectively inhibited memapsin 1 as well.

4 Although memapsin 1 hydrolyzes the beta-secretase site of APP, it

5 Memapsin 1 is closely homologous to memapsin 2 (BACE), o

6 report here the residue specificity of eight memapsin 1 subsites.

7 BACE2 (Memapsin 1) is a membrane-bound aspartic protease that i

8 inst mempasin 2 and good selectivity against memapsin 1.

9 an also be accommodated in these subsites of memapsin 1.

10 s of this therapy, we demonstrated that anti-memapsin 2 (anti-M2) antibodies were rapidly internalize

11 Memapsin 1 is closely homologous to memapsin 2 (BACE), or beta-secretase, whose action on be

12 Memapsin 2 (BACE, beta-secretase) is a membrane-associat

13 Memapsin 2 (beta-secretase) is a membrane-associated asp

14 Memapsin 2 (beta-secretase) is a membrane-associated asp

15 Memapsin 2 (beta-secretase) is one of two proteases that

16 Memapsin 2 (beta-secretase) is the membrane-anchored asp

17 Memapsin 2 (beta-secretase) is the protease that initiat

18 three-dimensional structure of unbound human memapsin 2 (beta-secretase) protease domain determined a

19 Memapsin 2 (beta-secretase), a membrane-anchored asparti

20 Memapsin 2 (beta-secretase, BACE1) is the protease that

21 here that the addition of the ectodomain of memapsin 2 (M2(ED)) to cells transfected with native APP

22 Recombinant memapsin 2 also cleaved a peptide derived from the proce

23 n the trans-Golgi network and endosomes with memapsin 2 and a memapsin 2 chimera containing a cytosol

24 Both memapsin 2 and APP are transported from the cell surface

25 Both memapsin 2 and APP are transported from the cell surface

26 In addition, full-length memapsin 2 and APP, immunoprecipitated together from cel

27 ggests that it is synthesized in vivo as pro-memapsin 2 and converted to memapsin 2 by an activating

28 rongly influences the hydrolytic activity by memapsin 2 and these subsites prefer hydrophobic residue

29 ces are strikingly similar to those of human memapsin 2 and thus pose a serious problem to the design

30 Both APP and memapsin 2 are Type I transmembrane proteins and are end

31 e structure of the catalytic domain of human memapsin 2 bound to an inhibitor OM00-3 (Glu-Leu-Asp-Leu

32 is essentially the same as the structure of memapsin 2 bound to an inhibitor, the flap positions are

33 d in vivo as pro-memapsin 2 and converted to memapsin 2 by an activating protease.

34 vestigated the activation of recombinant pro-memapsin 2 by several proteases with trypsin-like specif

35 The protease domain of memapsin 2 cDNA was expressed in Escherichia coli and wa

36 network and endosomes with memapsin 2 and a memapsin 2 chimera containing a cytosolic domain of a ma

37 APP and memapsin 2 in HeLa cells showed that memapsin 2 cleaved the beta-secretase site of APP intrac

38 al structure of the protease domain of human memapsin 2 complexed to an eight-residue inhibitor at 1.

39 A crystal structure of memapsin 2 complexed with a statine-based inhibitor span

40 ibed previously that the cytosolic domain of memapsin 2 contains an acid cluster-dileucine motif (ACD

41 reviously shown that the cytosolic domain of memapsin 2 contains an acid-cluster-dileucine (ACDL) mot

42 These and other results suggest that memapsin 2 fits all of the criteria of beta-secretase, w

43 ognition step for the vesicular packaging of memapsin 2 for its transport to endosomes.

44 ation mechanism and to produce stable mature memapsin 2 for kinetic/specificity studies, we have inve

45 s been reported to regulate the recycling of memapsin 2 from early endosomes back to the cell surface

46 The active site of memapsin 2 has been shown, with kinetic data and crystal

47 These results suggest that memapsin 2 immunization in Tg2576 was effective in reduc

48 not identified in the previous structure of memapsin 2 in complex with the inhibitor OM99-2 (Glu-Val

49 tion of ACDL resulted in the accumulation of memapsin 2 in early endosomes.

50 Expression of APP and memapsin 2 in HeLa cells showed that memapsin 2 cleaved

51 ynthesis of a number of potent and selective memapsin 2 inhibitors are described.

52 confirmed by the finding that several potent memapsin 2 inhibitors effectively inhibited memapsin 1 a

53 or the side-chain selection in the design of memapsin 2 inhibitors.

54 Memapsin 2 is a current target for the development of in

55 Reducing Abeta by targeting memapsin 2 is a major strategy in developing new AD ther

56 in the pathogenesis of Alzheimer's disease, memapsin 2 is an important target for the design of inhi

57 us, the intracellular transport mechanism of memapsin 2 is important for understanding the pathogenes

58 The active site of memapsin 2 is more open and less hydrophobic than that o

59 Memapsin 2 is the protease known as beta-secretase whose

60 A similar change of memapsin 2 localization also was observed when a retrome

61 Memapsin 2 mRNA is abundant in human brain.

62 er a potent active site binding inhibitor of memapsin 2 nor an antibody directed to the beta-secretas

63 These results also suggest that Glu(33p)-memapsin 2 observed in the cells expressing this enzyme

64 A crystal structure of the complex between memapsin 2 phosphoserine peptide and GGA1 VHS was solved

65 n-ligand X-ray crystal structure of 5d-bound memapsin 2 provided vital molecular insight that can ser

66 f peptides indicates that the specificity of memapsin 2 resides mainly at the S(1)' subsite, which pr

67 nization of transgenic AD mice (Tg2576) with memapsin 2 resulted in Abeta reduction and cognitive imp

68 A molecular model of OM00-3 binding to memapsin 2 revealed critical improvement of the interact

69 inhibitor, OM03-4 (K(i) = 0.03 nM), bound to memapsin 2 revealed the interaction of a tryptophan with

70 was found to be the most potent inhibitor of memapsin 2 so far reported (K(i) of 3.1 x 10(-10) M).

71 Recombinant memapsin 2 specifically hydrolyzed peptides derived from

72 e results establish that the activity of pro-memapsin 2 stems from a part-time and reversible uncover

73 The primary structure of memapsin 2 suggests that it is synthesized in vivo as pr

74 our subsites were also studied by binding of memapsin 2 to a combinatorial inhibitor library.

75 activated memapsin 2 were compared with pro-memapsin 2 using two new fluorogenic substrates, Arg-Glu

76 Kinetics of the activated memapsin 2 were compared with pro-memapsin 2 using two n

77 in cleaving enzyme (BACE1; also called Asp2, memapsin 2), is the enzyme responsible for initiating Ab

78 otease that is highly homologous with BACE1 (Memapsin 2).

79 BACE1 (beta-secretase, memapsin 2, Asp2) has emerged as a promising target for

80 ing of substrate APPsw to the active site of memapsin 2, because neither a potent active site binding

81 ssociated aspartic proteases, memapsin 1 and memapsin 2, have been cloned and sequenced.

82 Another activation product, Leu(28p)-memapsin 2, was also purified.

83 e designed based upon the X-ray structure of memapsin 2-bound inhibitor 3 that incorporates methylsul

84 function with the phosphorylated ACDL in the memapsin 2-recycling pathway from endosomes to trans-Gol

85 tosed into endosomes where APP is cleaved by memapsin 2.

86 surface to endosomes where APP is cleaved by memapsin 2.

87 y selective inhibitors capable of inhibiting memapsin 2.

88 ighest k(cat)/K(M) value so far observed for memapsin 2.

89 und aspartyl protease, named BACE1, Asp2, or memapsin 2.

90 e the residue preference for the subsites of memapsin 2.

91 egions of the enzyme active sites of 3-bound memapsin 2.

92 ide to the active site, results in activated memapsin 2.

93 activation products, Leu(30p)- and Gly(45p)-memapsin 2.

94 n, and trypsin increased the activity of pro-memapsin 2.

95 Here, we report a study on the memapsin 2/VHS domain interaction.

96 ced the molecular weight and designed potent memapsin inhibitors.

97 tor (2, OM99-2 with eight residues) bound to memapsin, we have reduced the molecular weight and desig