RNA ligase structures reveal the basis for RNA specificity and conformational changes that drive ligation forward Journal Article

  


Authors: Nandakumar, J.; Shuman, S.; Lima, C. D.
Article Title: RNA ligase structures reveal the basis for RNA specificity and conformational changes that drive ligation forward
Abstract: T4 RNA ligase 2 (Rnl2) and kinetoplastid RNA editing ligases exemplify a family of RNA repair enzymes that seal 3′OH/5′PO 4 nicks in duplex RNAs via ligase adenylylation (step 1), AMP transfer to the nick 5′PO 4 (step 2), and attack by the nick 3′OH on the 5′-adenylylated strand to form a phosphodiester (step 3). Crystal structures are reported for Rnl2 at discrete steps along this pathway: the covalent Rnl2-AMP intermediate; Rnl2 bound to an adenylylated nicked duplex, captured immediately following step 2; and Rnl2 at an adenylylated nick in a state poised for step 3. These structures illuminate the stereochemistry of nucleotidyl transfer and reveal how remodeling of active-site contacts and conformational changes propel the ligation reaction forward. Mutational analysis and comparison of nick-bound structures of Rnl2 and human DNA ligase I highlight common and divergent themes of substrate recognition that can explain their specialization for RNA versus DNA repair. © 2006 Elsevier Inc. All rights reserved.
Keywords: nonhuman; comparative study; dna repair; mutational analysis; rna; molecular sequence data; molecular recognition; substrate specificity; base sequence; crystal structure; models, molecular; crystallography, x-ray; protein structure, tertiary; binding sites; molecular structure; dna mutational analysis; adenosine triphosphate; nucleic acid conformation; enzyme specificity; enzyme structure; kinetoplast; model; rna ligase (atp); rna binding; stereochemistry; nucleoside; dna ligases; viral proteins; enzyme active site; enzyme conformation; adenylation; nucleotidyltransferase; rna analysis; adenosine monophosphate; covalent bond; rna ligase; rna conformation; kinetoplastida
Journal Title: Cell
Volume: 127
Issue: 1
ISSN: 0092-8674
Publisher: Cell Press  
Date Published: 2006-10-06
Start Page: 71
End Page: 84
Language: English
DOI: 10.1016/j.cell.2006.08.038
PUBMED: 17018278
PROVIDER: scopus
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-33749080322&partnerID=40&md5=a58f281d61e755e883a40abea8193f91
Notes: --- - "Cited By (since 1996): 26" - "Export Date: 4 June 2012" - "CODEN: CELLB" - "Source: Scopus"
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MSK Authors
  1. Jayakrishnan Nandakumar
    10 Nandakumar
  2. Stewart H Shuman
    546 Shuman
  3. Christopher D Lima
    103 Lima
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