Re: [ccp4bb] asymmetric oligomers

[Poul Nissen]

HIV reverse transcriptase - I've added the first reference, but many later studies will elucidate this further. Poul 1: Science. 1992 Jun 26;256(5065):1783-90. Links Crystal structure at 3.5 A resolution of HIV-1 reverse transcriptase complexed with an inhibitor. Kohlstaedt LA, Wang J, Friedman JM, Rice PA, Steitz TA. Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511. A 3.5 angstrom resolution electron density map of the HIV-1 reverse transcriptase heterodimer complexed with nevirapine, a drug with potential for treatment of AIDS, reveals an asymmetric dimer. The polymerase (pol) domain of the 66-kilodalton subunit has a large cleft analogous to that of the Klenow fragment of Escherichia coli DNA polymerase I. However, the 51-kilodalton subunit of identical sequence has no such cleft because the four subdomains of the pol domain occupy completely different relative positions. Two of the four pol subdomains appear to be structurally related to subdomains of the Klenow fragment, including one containing the catalytic site. The subdomain that appears likely to bind the template strand at the pol active site has a different structure in the two polymerases. Duplex A-form RNA-DNA hybrid can be model-built into the cleft that runs between the ribonuclease H and pol active sites. Nevirapine is almost completely buried in a pocket near but not overlapping with the pol active site. Residues whose mutation results in drug resistance have been approximately located. ======================================================== Poul Nissen, professor, ph.d. Centre for Membrane Pumps in Cells and Disease - PUMPKIN & Centre for Structural Biology University of Aarhus, Dept. Molecular Biology Gustav Wieds Vej 10C, DK - 8000 Aarhus C, Denmark http://www.mb.au.dk http://www.bioxray.au.dk http://www.pumpkin.au.dk http://person.au.dk/da/[EMAIL PROTECTED] Tel. +45 8942 5025 Mobile +45 2899 2295 Fax +45 8612 3178,  [EMAIL PROTECTED] On 22/09/2008, at 18.15, Kornelius Zeth wrote: Dear all, I'm searching for examples of crystal structures that show a clear asymmetry in the dimeric/oligomeric state. This asymmetry should not have been induced by the crystal packing (e.g. two domains connected by a long linker packing different, termini/loops which interact differently with the surrounding) rather than by an internal asymmetry (which may be confirmed by other techniques e.g. SAXS). The reason I'm asking: I have solved a couple of crystal structures of a chimera protein (110 residues, dimeric, 1.2 A resolution) and mutants of the same fragment consisting of basically two four helix bundles and a short connector fragment and these are highly asymmetric (although the H-bond pattern of the helix residues doesn't change) while the same structures solved by NMR are symmetric and largely different. PISA gives a variety of contacts (H-bonds, salt bridges) between the two chains, interface seems ok, stable, low B-factors). Any comments and suggestions are appreciated Best wishes and thanks! Kornelius ---------------------------------------------- Kornelius Zeth Max Planck Institute for Developmental Biology Dept. Protein Evolution Spemannstr. 35 72076 Tuebingen, Germany [EMAIL PROTECTED] Tel -49 7071 601 323 Fax -49 7071 601 349