Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.3.1 (citrate synthase)
 4,488 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The alpha isoform of human 90-kDa heat shock protein (HSP90alpha) is composed of three domains: the N-terminal (residues 1-400); middle (residues 401-615) and C-terminal (residues 621-732). The middle domain is simultaneously associated with the N- and C-terminal domains, and the interaction with the latter mediates the dimeric configuration of HSP90. Besides one in the N-terminal domain, an additional client-binding site exists in the C-terminal domain of HSP90. The aim of the present study is to elucidate the regions within the C-terminal domain responsible for the bindings to the middle domain and to a client protein, and to define the relationship between the two functions. A bacterial two-hybrid system revealed that residues 650-697 of HSP90alpha were essential for the binding to the middle domain. An almost identical region (residues 657-720) was required for the suppression of heat-induced aggregation of citrate synthase, a model client protein. Replacement of either Leu665-Leu666 or Leu671-Leu672 to Ser-Ser within the hydrophobic segment (residues 662-678) of the C-terminal domain caused the loss of bindings to both the middle domain and the client protein. The interaction between the middle and C-terminal domains was also found in human 94-kDa glucose-regulated protein. Moreover, Escherichia coli HtpG, a bacterial HSP90 homologue, formed heterodimeric complexes with HSP90alpha and the 94-kDa glucose-regulated protein through their middle-C-terminal domains. Taken together, it is concluded that the identical region including the hydrophobic segment of the C-terminal domain is essential for both the client binding and dimer formation of the HSP90-family molecular chaperone and that the dimeric configuration appears to be similar in the HSP90-family proteins.
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PMID:A hydrophobic segment within the C-terminal domain is essential for both client-binding and dimer formation of the HSP90-family molecular chaperone. 1249 85

This investigation evaluated the potential of natural antioxidants, pterostilbene (PT) and its parent compound resveratrol (RSV), to alleviate hepatic damage, redox imbalance, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress in early-weaned piglets. A total of 144 suckling piglets were randomly assigned to four treatments (six replicates per group, n = 6): 1) sow reared, 2) early weaned and fed a basal diet, 3) early weaned and fed the basal diet supplemented with 300 mg/kg PT, or with 4) 300 mg/kg RSV. Early weaning increased plasma alanine aminotransferase (P = 0.004) and aspartate aminotransferase (P = 0.009) activities and hepatic apoptotic rate (P = 0.001) in piglets compared with the sow-reared piglets. Early weaning decreased hepatic adenosine triphosphate (ATP; P = 0.006) content and mitochondrial complexes III (P = 0.019) and IV activities (P = 0.038), but it increased superoxide anion accumulation (P = 0.026) and the expression levels of ER stress markers, such as glucose-regulated protein 78 (P < 0.001), CCAAT/enhancer-binding protein-homologous protein (P = 0.001), and activating transcription factor (ATF) 4 (P = 0.006). PT was superior to RSV at mitigating liver injury and oxidative stress after early weaning, as indicated by decreases in the number of apoptotic cells (P = 0.036) and the levels of superoxide anion (P = 0.002) and 8-hydroxy-2 deoxyguanosine (P < 0.001). PT increased mitochondrial deoxyribonucleic acid content (P = 0.031) and the activities of citrate synthase (P = 0.005), complexes I (P = 0.004) and III (P = 0.011), and ATP synthase (P = 0.041), which may contribute to the mitigation of hepatic ATP deficit (P = 0.017) in the PT-treated weaned piglets. PT also prevented increases in the ER stress marker and ATF 6 expression levels and in the phosphorylation of inositol-requiring enzyme 1 alpha caused by early weaning (P < 0.05). PT increased sirtuin 1 activity (P = 0.031) in the liver of early-weaned piglets than those in the early-weaned piglets fed a basal diet. In conclusion, PT supplementation alleviates liver injury in weanling piglets probably by inhibiting mitochondrial dysfunction and ER stress.
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PMID:Protective effects of pterostilbene against hepatic damage, redox imbalance, mitochondrial dysfunction, and endoplasmic reticulum stress in weanling piglets. 3302 17