Genmab A/S - Company Announcement: Novel Insights into HuMax-EGFr Mechanisms of Action Published in PNAS Apr 16, 2008
Biochemical analyses showed that HuMax-EGFr binds bivalently to the EGFr and, furthermore, was shown to prevent receptor dimerization and to severely limit intermolecular flexibility of EGFr molecules. "These new insights point out that HuMax-EGFr may employ at least three distinct mechanisms of action leading to inhibition of cancer cell growth. HuMax-EGFr is able to induce potent immune system defense activity known as ADCC, block growth factor binding to EGF receptors, and we now established... (PR Newswire)
Immunomedics Creates Novel Cytokine Immunoconjugates Using Dock-and-Lock Apr 16, 2008
DNL employs two building units: the dimerization and docking domain (DDD) module and the anchoring domain (AD) module for the creation of protein complexes ... The region that is involved in such interaction for PKA is called the dimerization and docking domain (DDD), which always appears in pairs. (Primezone Releases)
Media highlights in the November issues of Biophysical Journal Nov 1, 2007
Since the function of NhaA critically depends on dimerization, the dimer structure provides new insight into the mechanism of ion transportation through cell membranes by this protein. . (EurekAlert!)
Crystal structure of hyperthermophilic esterase EstE1 and the relationship between its dimerization and thermostability properties Jul 12, 2007
Circular dichroism spectroscopy and heat inactivation kinetic analysis of EstE1 mutants, which were generated by structure-based site-directed mutagenesis of amino acid residues participating in EstE1 dimerization, revealed that hydrophobic interactions through Val274 and Phe276 on the 8 strand of each monomer play a major role in the dimerization of EstE1. In contrast, the intermolecular salt bridges contribute less significantly to the dimerization and thermostability of EstE1. (BioMed Central)
Potential New Cancer Drug Target Identified Jun 23, 2007
"It interacts with another key protein, called TAB1, and it also interacts on a structural level with itself a process called dimerization," the researcher explains. Since both of these two activities might be vulnerable to some kind of pharmaceutical interference or interruption, they present promising new targets for the development of anti-cancer drugs. (Science Daily)
The chemokine, Sdf-1, and its receptor, Cxcr4, are required for formation of muscle in zebrafish May 22, 2007
In addition, we showed that a dimerization partner of MyoD and Myf5, E12, positively regulates transcription of cxcr4a and sdf1a in contrast to that of Sonic hedgehog, which inhibited these genes through induction of expression of id2. Conclusions. (BioMed Central)
New class of targeted cancer drugs shows promise in slowing progression of recurrent prostate cancer Feb 17, 2007
If the pairing process (called dimerization) is not interrupted, the binding of these growth factors activates an intracellular signaling pathway that leads to tumor proliferation. While other drugs such as docetaxel have shown to benefit men with advanced prostate cancer, no other second-line therapy (a treatment given when an initial treatment (first-line therapy) does not work or stops working) to date has shown to prolong survival. (EurekAlert!)
Structure of a conserved hypothetical protein SA1388 from S. aureus reveals a capped hexameric toroid with two PII domain lids and a dinuclear metal center Dec 24, 2006
The N and C terminal halves of the NIF3-like domains are involved in dimerization, while the PII domain forms trimeric contacts with symmetry related monomers. Overall, the NIF3-like domains of SA1388 are organized as a hexameric toroid similar to its homologs, E. coli ybgI and the hypothetical protein SP1609 from Streptococcus pneumoniae. (BioMed Central)
GPCRs may not pair up as often as thought Nov 10, 2006
The controversial new results suggest prior studies may have mistaken random interactions for true dimerizations ... "I think many of the best people in the field do consider that a lot of relatively poor papers have been produced, particularly in studies examining hetero-dimerization. Of course, key experiments now require the presence of dimers to be shown unequivocally in native tissues," he told The Scientist in an email ... Despite this, "I feel that this manuscript fails to consider the... (The Scientist)
