Abstract：
:Our computer simulations of gamma glutamyl semialdehyde dehydrogenase (GGSALDH, pyrroline 5-carboxylate dehydrogenase, ALDH4) were initiated from the Thermus thermophilus crystal structures in an effort to understand the effects of a seemingly subtle mutation. In humans, a natural S352L mutation gives rise to type II hyperprolinemia (mental retardation). The mutation occurs in what might be a priori considered the outer shell of the active site, affecting a residue of no obvious significance. In another member of the superfamily (ALDH3) this serine residue is an aspartate, which tethers the "distal" Lys. It has been our hypothesis that in ALDH3 this is a beneficial interaction, enabling the "proximal" Lys to interact with the carbonyl oxygen of the peptide bond with the catalytic Cys, allowing the Cys amide N to transiently protonate the tetrahedral intermediate. That the role of this Asp is significant is proved by a natural Asp-to-Asn mutation that abolishes activity. The Ser-to-Leu exchange in GGSALDH might be expected to alter the water structure at the site of mutation, and the MM simulations clearly support this. It was our hypothesis, based on initial static models of the mutation, that the leucyl side chain would block the direct or indirect interaction of the distal Lys with the active site. Our simulations indicate that this lysine residue is indeed important in explaining the molecular pathology of the mutation. Through small rotations of its C-C bonds, the Lys epsilon-amino group comes into H-bonding distance with Ser-326, the equivalent of human Ser-352. In the S326L mutant, this interaction is not possible, while the water network from this residue to the target main-chain carbonyl oxygen is disturbed as well.
journal_name
Chem Biol Interactjournal_title
Chemico-biological interactionsauthors
Hempel J,Kraut A,Wymore Tdoi
10.1016/j.cbi.2008.10.009subject
Has Abstractpub_date
2009-03-16 00:00:00pages
75-8issue
1-3eissn
0009-2797issn
1872-7786pii
S0009-2797(08)00551-6journal_volume
178pub_type
杂志文章abstract：:Tetrachlorohydroquinone (TCHQ), which has previously been identified as a metabolite of pentachlorophenol, induces DNA strand breaks in isolated DNA and in human fibroblasts. Strand break formation in PM2 DNA is prevented by the addition of catalase and the hydroxyl radical scavengers DMSO, ethanol and mannitol, where...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(90)90047-q
更新日期：1990-01-01 00:00:00
abstract：:Pogostemonis Herba is an important Chinese medicine widely used in the treatment of gastrointestinal dysfunction. Patchouli alcohol (PA), a tricyclic sesquiterpene, is the major active constituent of Pogostemonis Herba. This study aimed to investigate the possible anti-ulcerogenic potential of PA and the underlying me...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2014.08.008
更新日期：2014-10-05 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(75)90100-3
更新日期：1975-09-01 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(80)90075-7
更新日期：1980-10-01 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2020.109251
更新日期：2020-10-01 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章,评审
doi：10.1016/0009-2797(94)90034-5
更新日期：1994-06-01 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(92)90029-k
更新日期：1992-01-01 00:00:00
abstract：:The mechanisms involved in the cytotoxicity of 2-bromo-3-(N-acetylcystein-S-yl)hydroquinone, a model compound for hydroquinone derived mercapturic acids, were investigated in rat renal proximal tubule cells. 2-Bromo-3-(N-acetylcystein-S-yl)hydroquinone induced a time- and concentration-dependent decrease in cell viabi...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(92)90045-m
更新日期：1992-08-14 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2008.07.005
更新日期：2008-11-25 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2015.11.011
更新日期：2016-01-05 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2006.01.002
更新日期：2006-03-25 00:00:00
abstract：:20(S)-protopanaxadiol (PPD) possesses various biological properties, including anti-inflammatory, antitumor and anti-fatigue properties. Recent studies found that PPD functioned as a neurotrophic agent to ameliorate the sensory deficit caused by glutamate-induced excitotoxicity through its antioxidant effects and exhi...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2017.11.008
更新日期：2018-01-05 00:00:00
abstract：:Irinotecan is highly effective in the treatment of metastatic colorectal cancer as well as many other cancers. However, irinotecan is known to cause severe diarrhea, which pose significant problems in patients undergoing irinotecan based chemotherapy. Dietary and herbal components have shown promise in improving gastr...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2018.06.018
更新日期：2018-08-01 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2011.10.004
更新日期：2012-01-05 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2016.01.011
更新日期：2016-03-25 00:00:00
abstract：:A few organophosphorus compounds (OPs) can cause toxic neuropathy known as organophosphorus ester-induced delayed neuropathy (OPIDN). Although the incidents of OPIDN have been documented for over a century, its molecular mechanisms underlying the axonopathy are still unclear. Recently, increasing evidences suggest tha...
journal_title：Chemico-biological interactions
pub_type： 杂志文章,评审
doi：10.1016/j.cbi.2012.10.001
更新日期：2012-12-05 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2011.02.002
更新日期：2011-04-25 00:00:00
abstract：:Acetaminophen hepatotoxicity is characterized by extensive necrotic cell death and a sterile inflammatory response. A recent report suggested that a therapeutic intervention with chlorogenic acid, a dietary polyphenolic compound, protects against acetaminophen-induced liver injury by inhibiting the inflammatory injury...
journal_title：Chemico-biological interactions
pub_type： 信件
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更新日期：2016-01-05 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章,评审
doi：10.1016/s0009-2797(97)00148-8
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
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更新日期：2019-04-01 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(97)00074-4
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2015.11.008
更新日期：2016-08-05 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(01)00226-5
更新日期：2001-08-31 00:00:00
abstract：:L-Xylulose reductase (XR) catalyzes the oxidoreduction between xylitol and L-xylulose in the uronate cycle. The enzyme has been shown to be identical to diacetyl reductase, an enzyme that reduces alpha-dicarbonyl compounds. XR belongs to the short-chain dehydrogenase/reductase family, and shows high sequence identity ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(02)00217-x
更新日期：2003-02-01 00:00:00
abstract：:ATP mediates covalent binding of hydroxymethyl derivatives of aromatic hydrocarbons to DNA. This non-enzymatic reaction has been studied with 6-[14C]hydroxymethylbenzo[alpha]pyrene (]14C]BP-6-CH2OH) and 7-[14C]-hydroxymethylbenz[alpha]anthracene ([14C]BA-7-CH2OH) at 37 degrees C in Tris buffer (pH 7.0). While ADP medi...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(80)90138-6
更新日期：1980-07-01 00:00:00
abstract：:Dopa was oxidized by Mn(3+)-pyrophosphate complex to the corresponding o-quinone, accompanied by the cyclization of the amino chain to form cyclized dopa ortho-quinone (cDoQ) with absorption maxima at wavelengths of 305 and 475 nm. The cyclization was found to proceed in a single step from DoQ to cDoQ without formatio...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(94)90090-6
更新日期：1994-11-01 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(82)90134-x
更新日期：1982-11-01 00:00:00
abstract：:In Alzheimer's disease (AD) a reduction in acetylcholinesterase (AChE) and an increase in butyrylcholinesterase (BChE) activity are observed. K variant (539T) is the most common variant of the BCHE gene and, although controversial, several studies reported association between K variant and AD. Previous results showed ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2012.09.008
更新日期：2013-03-25 00:00:00
abstract：:Until the last decade, two unrelated aldehyde dehydrogenase (ALDH) superfamilies, i.e. the phosphorylating and non-phosphorylating superfamilies, were known to catalyze the oxidation of aldehydes to activated or non-activated acids. However, a third one was discovered by the crystal structure of a bifunctional enzyme ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2012.11.006
更新日期：2013-02-25 00:00:00
abstract：:Passive paracellular absorption, regulated by tight junctions (TJs), is the main route for absorption of poorly absorbed hydrophilic substances. Surface active substances, such as fatty acids, may enhance absorption of these substances by affecting the integrity of TJ and increasing the permeability. It has been sugge...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2009.06.016
更新日期：2009-10-07 00:00:00
