1k1f
From Proteopedia
Structure of the Bcr-Abl Oncoprotein Oligomerization domain
Structural highlights
DiseaseBCR_HUMAN Note=A chromosomal aberration involving BCR is a cause of chronic myeloid leukemia. Translocation t(9;22)(q34;q11) with ABL1. The translocation produces a BCR-ABL found also in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). FunctionBCR_HUMAN GTPase-activating protein for RAC1 and CDC42. Promotes the exchange of RAC or CDC42-bound GDP by GTP, thereby activating them. Displays serine/threonine kinase activity.[1] [2] Publication Abstract from PubMedThe Bcr-Abl oncoprotein is responsible for a wide range of human leukemias, including most cases of Philadelphia chromosome-positive chronic myelogenous leukemia. Oligomerization of Bcr-Abl is essential for oncogenicity. We determined the crystal structure of the N-terminal oligomerization domain of Bcr-Abl (residues 1-72 or Bcr1-72) and found a novel mode of oligomer formation. Two N-shaped monomers dimerize by swapping N-terminal helices and by forming an antiparallel coiled coil between C-terminal helices. Two dimers then stack onto each other to form a tetramer. The Bcr1-72 structure provides a basis for the design of inhibitors of Bcr-Abl transforming activity by disrupting Bcr-Abl oligomerization. Structure of the Bcr-Abl oncoprotein oligomerization domain.,Zhao X, Ghaffari S, Lodish H, Malashkevich VN, Kim PS Nat Struct Biol. 2002 Feb;9(2):117-20. PMID:11780146[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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