caa a22 4500 475846176 CHVBK 20180406123914.0 cr unu---uuuuu 170329e20000501xx s 000 0 eng 10.1007/s000180050047 doi (NATIONALLICENCE)springer-10.1007/s000180050047 Three-dimensional model of human TIP30, a coactivator for HIV-1 Tat-activated transcription, and CC3, a protein associated with metastasis suppression [Elektronische Daten] [M. E. Baker*, L. Yan, M. R. Pear] Abstract.: Human TIP30 is a cofactor that specifically enhances human immunodeficiency virus-1 (HIV-1) Tat-activated transcription. The sequence of TIP30 is identical to that of CC3, a protein associated with metastasis suppression. TIP30/CC3 is a member of the short-chain dehydrogenases/reductases (SDR) family. Of the several experimentally determined SDR structures, Escherichia coli uridine diphosphate (UDP) galactose-4 epimerase is most similar to TIP30/CC3. Because the direct sequence similarity between TIP30/CC3 and E. coli UDP galactose-4 epimerase is low, we used the transitive nature of homology and employed two Aquifex aeolicus proteins as intermediaries in the homology modeling process. Comparison of our structural model with that of known SDRs reveals that TIP30/CC3 contains several well-conserved features, including a βαβ fold at the amino terminus, which we predict binds NADP(H). TIP30/CC3 contains characteristic motifs at the catalytic site of SDRs, including a serine, tyrosine, and lysine that are important in catalyzing hydride transfer between substrate and cofactor. We also predict that a unique 20-amino acid sequence found at the amino terminus is an α-helix. Because this region contains several positively and negatively charged amino acids, it may dock TIP30/CC3 to other proteins. Our structural model points to this α-helix and the SDR-like part of TIP30/CC3 for mutagenesis experiments to elucidate its role in HIV-1 Tat-activated transcription, metastasis suppression, and other cellular functions. Birkhäuser Verlag Basel,, 2000 Key words. HIV-1 nationallicence Tat nationallicence metastasis nationallicence TIP30 nationallicence CC3 nationallicence Baker* M. E. Department of Medicine, 0823, University of California, San Diego, 9500 Gilman Drive, La Jolla (California 92093-0823, USA), Fax +1 619 543 7069, e-mail: mbaker@ucsd.edu, US aut Yan L. Molecular Simulations Inc., 9685 Scranton Road, San Diego (California 92121-3752, USA), e-mail: lly@msi.cou.michaelpear@home.com, US aut Pear M. R. Molecular Simulations Inc., 9685 Scranton Road, San Diego (California 92121-3752, USA), e-mail: lly@msi.cou.michaelpear@home.com, US aut https://doi.org/10.1007/s000180050047 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s000180050047 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Baker* M. E. Department of Medicine, 0823, University of California, San Diego, 9500 Gilman Drive, La Jolla (California 92093-0823, USA), Fax +1 619 543 7069, e-mail: mbaker@ucsd.edu, US aut NATIONALLICENCE 700 1- Yan L. Molecular Simulations Inc., 9685 Scranton Road, San Diego (California 92121-3752, USA), e-mail: lly@msi.cou.michaelpear@home.com, US aut NATIONALLICENCE 700 1- Pear M. R. Molecular Simulations Inc., 9685 Scranton Road, San Diego (California 92121-3752, USA), e-mail: lly@msi.cou.michaelpear@home.com, US aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer