PDB ID: 1A36
Number of Polypeptide Chains in the Protein: 3
Chain 1: B; Chain 2: C; Chain 3: A;
PDB Deposition Title:
TOPOISOMERASE I/DNA COMPLEX
Primary Citation Title:
A model for the mechanism of human topoisomerase I
Stewart, L., Redinbo, M.R., Qiu, X., Hol, W.G., Champoux, J.J.
Journal: (1998) Science 279: 1534-1541
Related PDB Entries:
Information for Chain A; UniprotKB Accession Number: P11387
Length of the Chain (from Uniprot P11387): 765
FASTA Sequence for the chain (from Uniprot P11387):
>sp|P11387|TOP1_HUMAN DNA topoisomerase 1 OS=Homo sapiens GN=TOP1 PE=1 SV=2
Secondary Structures (DSSP defined; from RCSB PDB)
Helical Structures: Number of Helices: 24; Percentage of Residues: 47
Beta Strands: Number of Strands: 21; Percentage of Residues: 11
Secondary Structure Map:
Number of Domains Along Chain A: 4
CATH Domain IDs: 1a36A01, 1a36A02, 1a36A03, 1a36A04
CATH Classes: A01: Mainly Beta, A02: Mainly Alpha, A03: Mainly Beta, A04: Mainly Alpha
CATH Architectures: A01: Beta Complex, A02: Orthogonal Bundle, A03: Alpha-Beta Complex, A04: Orthogonal Bundle
CATH Topologies: A01: DNA Topoisomerase I; domain 2, A02: Arc Repressor Mutant, subunit A, A03: Topoisomerase I; Chain A, domain 3, A04: Topoisomerase I; Chain A, domain 4
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Function and Ligand Binding Site
Excerpt from Abstract:
In combination with the crystal structures of the reconstituted human topoisomerase I before and after DNA cleavage, this information suggests which amino acid residues are involved in catalyzing phosphodiester bond breakage and religation. The structures also lead to the proposal that the topoisomerization step occurs by a mechanism termed "controlled rotation."
Description of Function from Uniprot:
Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free DNA strand then undergoes passage around the unbroken strand thus removing DNA supercoils. Finally, in the religation step, the DNA 5'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone (By similarity). Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. Involved in the circadian transcription of the core circadian clock component ARNTL/BMAL1 by altering the chromatin structure around the ROR response elements (ROREs) on the ARNTL/BMAL1 promoter. Catalytic ATP-independent breakage of single-stranded DNA, followed by passage and rejoining.
Selected Molecular Function GO Terms:
GO ID; 0003677, DNA binding Definition: Any molecular function by which a gene product interacts selectively and non-covalently with DNA (deoxyribonucleic acid).||
GO ID; 0003917, DNA topoisomerase type I activity Definition: Catalysis of a DNA topological transformation by transiently cleaving one DNA strand at a time to allow passage of another strand; changes the linking number by +1 per catalytic cycle.||
GO ID; 0003918, DNA topoisomerase (ATP-hydrolyzing) activity Definition: Catalysis of a DNA topological transformation by transiently cleaving a pair of complementary DNA strands to form a gate through which a second double-stranded DNA segment is passed, after which the severed strands in the first DNA segment are rejoined; product release is coupled to ATP binding and hydrolysis; changes the linking number in multiples of 2.
EC Number: EC 126.96.36.199
An isomerase which contains other isomerases, whose sole sub-subclass for isomerases does not belong in the other.
Major Organic Ligand: Deoxyribonucleic acid (DNA), ribonucleic acid (RNA)
Ligand Binding Residues:
Lys 216, His 266, Lys 354, Glu 356, Pro 357, Phe 361, Arg 362, Gly 363, Arg 364, His 367, Lys 374, Arg 405, Val 410, Tyr 411, Trp 412, Gln 421, Ile 424, Lys 425, Tyr 426, Met 428, Lys 436, Lys 439, Lys 443, Arg 488, Ala 489, Gly 490, Asn 491, Lys 493, Thr 498, Thr 501, Gly 531, Lys 532, Asp 533, Ile 535, Asn 574, Gln 578, Thr 585, Ala 586, Lys 587, Arg 590, His 632, Gln 633, Ser 643, Lys 650, Arg 708, Thr 718, Asn 722, Phe 723, Asn 745, Lys 746, Thr 747