1ej9
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:1ej9.gif|left|200px]] | [[Image:1ej9.gif|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_1ej9", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | + | or leave the SCENE parameter empty for the default display. | |
| - | | | + | --> |
| - | | | + | {{STRUCTURE_1ej9| PDB=1ej9 | SCENE= }} |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''CRYSTAL STRUCTURE OF HUMAN TOPOISOMERASE I DNA COMPLEX''' | '''CRYSTAL STRUCTURE OF HUMAN TOPOISOMERASE I DNA COMPLEX''' | ||
| Line 29: | Line 26: | ||
[[Category: Hol, W G.]] | [[Category: Hol, W G.]] | ||
[[Category: Redinbo, M R.]] | [[Category: Redinbo, M R.]] | ||
| - | [[Category: | + | [[Category: Human]] |
| - | [[Category: | + | [[Category: Protein-dna complex]] |
| - | [[Category: | + | [[Category: Type i topoisomerase]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 15:10:07 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 12:10, 2 May 2008
CRYSTAL STRUCTURE OF HUMAN TOPOISOMERASE I DNA COMPLEX
Overview
Human topoisomerase I helps to control the level of DNA supercoiling in cells and is vital for numerous DNA metabolic events, including replication, transcription, and recombination. The 2.6 A crystal structure of human topoisomerase I in noncovalent complex with a DNA duplex containing a cytosine at the -1 position of the scissile strand rather than the favored thymine is reported. The hydrogen bond between the O2 position of this -1 base and the epsilon-amino of the conserved Lys-532 residue, the only base-specific contact observed previously in the human topoisomerase I-DNA interaction, is maintained in this complex. Several unique features of this structure, however, have implications for the DNA-binding and active-site mechanisms of the enzyme. First, the ends of the DNA duplex were observed to shift by up to 5.4 A perpendicular to the DNA helical axis relative to structures reported previously, suggesting a novel degree of plasticity in the interaction between human topoisomerase I and its DNA substrate. Second, 12 additional residues at the NH(2) terminus of the protein (Trp-203-Gly-214) could be built in this structure, and they were found to pack against the putative hinge region implicated in the clamping of the enzyme around duplex DNA. Third, a water molecule was observed adjacent to the scissile phosphate and the active-site residues; the potential specific base character of this solvent molecule in the active-site mechanism of the enzyme is discussed. Fourth, the scissile phosphate group was found to be rotated by 75 degrees, bringing Lys-532 into hydrogen-bonding distance of one of the nonbridging phosphate oxygens. This orientation of the scissile phosphate group implicates Lys-532 as a fifth active-site residue, and also mimics the orientation observed for the 3'-phosphotyrosine linkage in the covalent human topoisomerase I-DNA complex structure. The implications of these structural features for the mechanism of the enzyme are discussed, including the potential requirement for a rotation of the scissile phosphate group during DNA strand cleavage and covalent attachment.
About this Structure
1EJ9 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Novel insights into catalytic mechanism from a crystal structure of human topoisomerase I in complex with DNA., Redinbo MR, Champoux JJ, Hol WG, Biochemistry. 2000 Jun 13;39(23):6832-40. PMID:10841763 Page seeded by OCA on Fri May 2 15:10:07 2008
