ライフサイエンスコーパス: CAIR

1 CAIR binds to the free enzyme up to 200-fold more tightl

2 CAIR-1 sequence is identical, save 2 amino acids, to BAG

3 CAIR-1/BAG-3 contains several PXXP SH3 binding domains l

4 CAIR-1/BAG-3 forms an EGF-regulated ternary complex with

5 CAIR-1/BAG-3 from control and EGF-treated cell lysates b

6 CAIR-1/BAG-3 is phosphorylated in vivo in the absence of

7 y-AIR (N(5)-CAIR) synthetase (PurK) and N(5)-CAIR mutase (class I PurE).

8 Here we report the X-ray structures of N(5)-CAIR synthetase from Escherichia coli with either MgATP

9 Since the reaction mechanism of N(5)-CAIR synthetase is believed to proceed via a carboxyphos

10 ctural analysis of Aspergillus clavatus N(5)-CAIR synthetase solved in the presence of either Mg(2)AT

11 inoimidazole ribonucleotide synthetase (N(5)-CAIR synthetase) converts 5-aminoimidazole ribonucleotid

12 inoimidazole ribonucleotide synthetase (N(5)-CAIR synthetase), a key enzyme in microbial de novo puri

13 g, we propose a catalytic mechanism for N(5)-CAIR synthetase.

14 CAIR) by two enzymes: N(5)-carboxy-AIR (N(5)-CAIR) synthetase (PurK) and N(5)-CAIR mutase (class I Pu

15 tide (AIR), MgATP, and bicarbonate into N(5)-CAIR, MgADP, and P(i).

16 tance by Asp 153, attacks CO(2) to form N(5)-CAIR.

17 aminoimidazole ribonucleotide (AIR) to N(5)-CAIR.

18 that TdPurE binds AIR and CO(2) but not N(5)-CAIR.

19 troaminoimidazole ribonucleotide (NO2-AIR, a CAIR analogue) and structures of H45N and H45Q PurEs soa

20 li, the latter being the first instance of a CAIR-ligated SAICAR synthetase.

21 D-ribofuranosyl)imidazole-4-carboxylic acid (CAIR) along a reaction sequence involving a tandem N-for

22 The ADP.CAIR complex is the basis for a transition state model o

23 he crystal structures of the ADP and the ADP.CAIR complexes of SAICAR synthetase from Escherichia col

24 leotide (AIR) is converted to 4-carboxy-AIR (CAIR) by two enzymes: N(5)-carboxy-AIR (N(5)-CAIR) synth

25 azole ribonucleotide (AIR) to 4-carboxy-AIR (CAIR) represents an unusual divergence in purine biosynt

26 ADP and CAIR bind to the active site in association with three M

27 onism, with the strongest antagonism between CAIR and either ATP or L-aspartate.

28 -carboxyl and 5-amino groups of enzyme-bound CAIR.

29 H3 interaction, PLC-gamma was pulled down by CAIR-1/BAG-3 PXXP-GST fusions, but GST-PXXP constructs c

30 nd 5-aminoimidazole-4-carboxyribonucleotide (CAIR) to 5-aminoimidazole-4-(N-succinylcarboxamide) ribo

31 complex and that the inhibitory co-chaperone CAIR-1 functions distal to client ubiquitination.

32 nSO4 stopping reagent is proposed to chelate CAIR, enabling delayed analysis of this acid-labile prod

33 purE gene, the hallmarks of CO(2)-dependent CAIR synthesis.

34 , buried carboxylate or CO2 binding site for CAIR and N5-CAIR in a hydrophobic pocket in which the ca

35 N5-CAIR is transferred directly to generate CAIR without equilibration with CO2/HCO3- in solution.

36 lation in the forward direction (N5-CAIR --> CAIR).

37 a mechanism for the purE-catalyzed N5-CAIR-->CAIR biosynthetic one that involves a carboxylative sp3-

38 of the inactive mutant H59N-AaPurE soaked in CAIR showed that protonation of CAIR C4 can occur in the

39 of a phosphoryl transfer reaction involving CAIR and ATP, but also supports an alternative chemical

40 engineered to overexpress either full-length CAIR-1 (FL), which binds Hsp70, or a BAG domain-deletion

41 er with a reasonable mechanism for the model CAIRs-->FAIRs synthetic transformation is interpreted to

42 echanism of this rearrangement, [4,7-13C]-N5-CAIR and [7-14C]-N5-CAIR were synthesized and separately

43 rrangement, [4,7-13C]-N5-CAIR and [7-14C]-N5-CAIR were synthesized and separately incubated with PurE

44 supported by DFT calculations on CAIR and N5-CAIR analogues in which the ribose 5'-phosphate is repla

45 boxylate or CO2 binding site for CAIR and N5-CAIR in a hydrophobic pocket in which the carboxylate or

46 upport a mechanism for the purE-catalyzed N5-CAIR-->CAIR biosynthetic one that involves a carboxylati

47 interconversion of acid-labile compounds N5-CAIR and 4-carboxy-5-aminoimidazole ribonucleotide (CAIR

48 decarboxylation in the forward direction (N5-CAIR --> CAIR).

49 boxyaminoimidazole ribonucleotide mutase (N5-CAIR mutase or PurE) from Escherichia coli catalyzes the

50 the carboxylate group of the carbamate of N5-CAIR is transferred directly to generate CAIR without eq

51 rE catalyzes the unusual rearrangement of N5-CAIR to CAIR.

52 catalyzed constitutional isomerization of N5-CAIR to CAIR.

53 talyzes the reversible interconversion of N5-CAIR to carboxyaminoimidazole ribonucleotide (CAIR) with

54 N5-carboxyaminoimidazole ribonucleotide (N5-CAIR) in a reaction that requires both ATP and HCO3-.

55 N5-carboxyaminoimidazole ribonucleotide (N5-CAIR) mutase (PurE) catalyzes the reversible interconver

56 N5-carboxyaminoimidazole ribonucleotide (N5-CAIR) synthetase, catalyzes the conversion of 5-aminoimi

57 bstrate for proton transfer from His45 to N5-CAIR to form an enzyme-bound aminoimidazole ribonucleoti

58 nucleotide (AIR), ATP, and bicarbonate to N5-CAIR, ADP, and Pi.

59 The expression of CAIR-1, CAI stressed-1, was induced in A2058 human melan

60 same oxygen atom of the 4-carboxyl group of CAIR; whereas, the third coordinates the alpha- and beta

61 ion, it is shown that the phosphorylation of CAIR takes place before the condensation reaction with t

62 rE soaked in CAIR showed that protonation of CAIR C4 can occur in the absence of His59.

63 thetic) direction PurE favors protonation of CAIR C4.

64 ons suggest that the nonaromatic tautomer of CAIR (isoCAIR) is only 3.1 kcal/mol higher in energy tha

65 The PurC trapping of CAIR as SAICAR was required because of the reversibility

66 ransfers is supported by DFT calculations on CAIR and N5-CAIR analogues in which the ribose 5'-phosph

67 a position to remove a C4 proton to produce CAIR.

68 f 4-carboxy-5-aminoimidazole ribonucleotide (CAIR) in the purine pathway in most prokaryotes requires

69 s 4-carboxy-5-aminoimidazole ribonucleotide (CAIR) to 4-(N-succinylcarboxamide)-5-aminoimidazole ribo

70 d 4-carboxy-5-aminoimidazole ribonucleotide (CAIR).

71 ion of carboxyaminoimidazole ribonucleotide (CAIR) and l-aspartate to N-succinylcarboxamide-5-aminoim

72 ted to carboxyaminoimidazole ribonucleotide (CAIR) by reaction with CO(2) and SAICAR synthetase (SAIC

73 AIR to carboxyaminoimidazole ribonucleotide (CAIR) with direct CO2 transfer.

74 We hypothesize that CAIR-1/BAG-3 inhibits Hsp-mediated proteasomal degradati

75 stin proteasomal inhibition, indicating that CAIR-1 inhibits proteasomal degradation distal to protei

76 We propose that CAIR-1/BAG-3 may act as a multifunctional signaling prot

77 We show that CAIR-1/BAG-3 binds to Hsp70/Hsc70 in intact cells and th

78 We show that CAIR-1/BAG-3 binds to PLC-gamma and Hsp70/Hsc70 through

79 The CAIR carboxylate derives from bicarbonate or CO(2), resp

80 In animals, the conversion of AIR to CAIR requires a single enzyme, AIR carboxylase (class II

81 PLC-gamma is bound to CAIR-1/BAG-3 in unstimulated cells.

82 yzes the unusual rearrangement of N5-CAIR to CAIR.

83 d constitutional isomerization of N5-CAIR to CAIR.

84 P is a competitive inhibitor with respect to CAIR, suggesting the possibility of a hydrogen bond inte

85 (2) and SAICAR synthetase (SAICARs) in which CAIR then reacts with an aspartate to form SAICAR, in an

86 cular, we report the structure of PAICS with CAIR bound in the active sites of both domains and SAICA

87 tructures of H45N and H45Q PurEs soaked with CAIR have been determined and provide the first insight