Crystal structure of shikimate kinase from Mycobacterium tuberculosis reveals the dynamic role of the LID domain in catalysis.


:Shikimate kinase (SK) and other enzymes in the shikimate pathway are potential targets for developing non-toxic antimicrobial agents, herbicides, and anti-parasite drugs, because the pathway is essential in the above species but is absent from mammals. The crystal structure of Mycobacterium tuberculosis SK (MtSK) in complex with MgADP has been determined at 1.8 A resolution, revealing critical information for the structure-based design of novel anti-M. tuberculosis agents. MtSK, with a five-stranded parallel beta-sheet flanked by eight alpha-helices, has three domains: the CORE domain, the shikimate-binding domain (SB), and the LID domain. The ADP molecule is bound with its adenine moiety sandwiched between the side-chains of Arg110 and Pro155, its beta-phosphate group in the P-loop, and the alpha and beta-phosphate groups hydrogen bonded to the guanidinium group of Arg117. Arg117 is located in the LID domain, is strictly conserved in SK sequences, is observed for the first time to interact with any bound nucleotide, and appears to be important in both substrate binding and catalysis. The crystal structure of MtSK (this work) and that of Erwinia chrysanthemi SK suggest a concerted conformational change of the LID and SB domains upon nucleotide binding.


J Mol Biol


Gu Y,Reshetnikova L,Li Y,Wu Y,Yan H,Singh S,Ji X





Has Abstract


2002-06-07 00:00:00














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    abstract::Two forms of three-dimensional crystals of the light-harvesting chlorophyll a/b protein complex from pea have been obtained. Crystals of one form grew as hexagonal plates measuring up to 150 micron across and 2 to 3 micron in thickness. Electron diffraction patterns of thin hexagonal plates showed sharp reflections to...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Kühlbrandt W

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  • Engineered oligomerization state of OmpF protein through computational design decouples oligomer dissociation from unfolding.

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    journal_title:Journal of molecular biology

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    authors: Naveed H,Jimenez-Morales D,Tian J,Pasupuleti V,Kenney LJ,Liang J

    更新日期:2012-05-25 00:00:00

  • Kinetic isotope effects reveal the presence of significant secondary structure in the transition state for the folding of the N-terminal domain of L9.

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    journal_title:Journal of molecular biology

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    authors: Sato S,Raleigh DP

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  • Dynamic Properties of Human α-Synuclein Related to Propensity to Amyloid Fibril Formation.

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    journal_title:Journal of molecular biology

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    authors: Fujiwara S,Kono F,Matsuo T,Sugimoto Y,Matsumoto T,Narita A,Shibata K

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  • Regulatory sequences in sigma 54 localise near the start of DNA melting.

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    journal_title:Journal of molecular biology

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    authors: Wigneshweraraj SR,Chaney MK,Ishihama A,Buck M

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  • Phosphorylation and mutation of phospholamban alter physical interactions with the sarcoplasmic reticulum calcium pump.

    abstract::Phospholamban physically interacts with the sarcoplasmic reticulum calcium pump (SERCA) and regulates contractility of the heart in response to adrenergic stimuli. We studied this interaction using electron microscopy of 2D crystals of SERCA in complex with phospholamban. In earlier studies, phospholamban oligomers we...

    journal_title:Journal of molecular biology

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    authors: Glaves JP,Trieber CA,Ceholski DK,Stokes DL,Young HS

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    pub_type: 杂志文章


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    pub_type: 杂志文章


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    pub_type: 杂志文章


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    pub_type: 杂志文章


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    pub_type: 杂志文章


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    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Díaz-López T,Dávila-Fajardo C,Blaesing F,Lillo MP,Giraldo R

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    pub_type: 杂志文章


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