Abstract：
:Itch, a member of the E6AP carboxy terminus (HECT) domain-containing family of ubiquitin E3 ligases, acts in concert with the ubiquitin activating enzyme (E1) and the ubiquitin conjugating enzyme (E2) to catalyze ubiquitylation of protein targets. This sub-family of E3s shares a 350 residue C-terminal HECT domain having a strictly conserved catalytic Cys, and recruiting its cognate ubiquitin-loaded E2. HECT domains possess intrinsic enzymatic activity, by accepting ubiquitin from an E2, forming a ubiquitin thiolester intermediate, and directly catalyzing ubiquitylation of the target protein. Several hypotheses have been proposed for the biochemical mechanism underlying the structural relationship of the HECT-E2 association and subsequent ubiquitin transfer. Nonetheless, a detailed characterization of the process is still missing. In this work, we have used molecular dynamic simulations, free energy calculations, protein modelling techniques and normal modes analysis to get a deeper characterization of the static and dynamical properties of this interaction mechanism. We hypothesize a correlated slow-frequency motion that involves two different hinge regions of the HECT domain. The identification of the amino acid residues responsible for the HECT-E2 interaction, and for the dynamical properties of the ubiquitin transfer process, may be of relevant interest for pharmacological and therapeutical purposes.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Raimondo D,Giorgetti A,Bernassola F,Melino G,Tramontano Adoi
10.1016/j.bcp.2008.08.026subject
Has Abstractpub_date
2008-12-01 00:00:00pages
1620-7issue
11eissn
0006-2952issn
1873-2968pii
S0006-2952(08)00593-5journal_volume
76pub_type
杂志文章abstract：:It has been reported that chelerythrine chloride, a benzophenanthridine alkaloid, with a wide variety of biologic effects stimulates the phosphorylation of an approximately 20 kDa protein present in the mitochondrial fraction of the rat retina. It has also been shown previously that both the serine and threonine resid...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(96)00202-x
更新日期：1996-07-26 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90254-g
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pub_type： 杂志文章
doi：10.1016/j.bcp.2008.01.010
更新日期：2008-04-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-01-26 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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更新日期：2013-02-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90118-x
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2009.04.028
更新日期：2009-08-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90275-9
更新日期：1987-09-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2012.07.026
更新日期：2012-10-15 00:00:00
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pub_type： 杂志文章
doi：10.1016/0006-2952(83)90004-7
更新日期：1983-09-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(84)90338-1
更新日期：1984-06-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2010.05.024
更新日期：2010-09-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90144-a
更新日期：1990-02-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(01)00600-1
更新日期：2001-06-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2008.03.009
更新日期：2008-06-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90044-2
更新日期：1994-08-17 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(83)90144-2
更新日期：1983-12-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90244-q
更新日期：1993-03-09 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2014.01.003
更新日期：2014-04-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2006.10.015
更新日期：2007-02-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90003-8
更新日期：1989-09-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2010.06.052
更新日期：2010-10-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2016.11.023
更新日期：2017-01-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(84)90315-0
更新日期：1984-02-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(96)00108-6
更新日期：1996-06-28 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2004.06.020
更新日期：2004-10-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2020.114043
更新日期：2020-11-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2009.12.012
更新日期：2010-05-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90029-6
更新日期：1982-04-01 00:00:00
abstract：:The International Diabetes Federation predicts that by 2045 the number of individuals afflicted with diabetes will increase to 629 million. Furthermore, ∼352 million individuals with impaired glucose tolerance are at increased risk for developing diabetes. Several mechanisms have been proposed for the onset of metabol...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2018.04.026
更新日期：2018-08-01 00:00:00
