RNA polymerase II coordinates co-transcriptional events by recruiting distinct sets of nuclear factors to specific stages of transcription via changes of phosphorylation patterns along its C-terminal domain (CTD). Although it has become increasingly clear that proline isomerization also helps regulate CTDassociated processes, the molecular basis of its role is unknown. Here, we report the structure of the Ser(P) 5 CTD phosphatase Ssu72 in complex with substrate, revealing a remarkable CTD conformation with the Ser(P) 5 -Pro 6 motif in the cis configuration. We show that the cis-Ser(P) 5 -Pro 6 isomer is the minor population in solution and that Ess1-catalyzed cis-trans-proline isomerization facilitates rapid dephosphorylation by Ssu72, providing an explanation for recently discovered in vivo connections between these enzymes and a revised model for CTD-mediated small nuclear RNA termination. This work presents the first structural evidence of a cisproline-specific enzyme and an unexpected mechanism of isomer-based regulation of phosphorylation, with broad implications for CTD biology. The C-terminal domain (CTD)2 of the largest subunit of RNA polymerase II (RNAPII) consists of multiple tandem heptad repeats, with the consensus sequence Y 1 S 2 P 3 T 4 S 5 P 6 S 7 , that serve as a flexible binding platform for nuclear factors (1). CTD-binding partners influence the initiation, elongation, and termination of transcription as well as a myriad of cotranscriptional processes (2). The recruitment of these activities is tied to the progress of the polymerase by cyclic phosphorylation and dephosphorylation of the CTD repeats. For example, phosphorylation at the Ser 5 position (Ser(P) 5 ) predominates at the 5Ј-end of genes, attracting CTD-binding partners that influence initiation complex formation, mRNA capping, and the transition into elongation (3). As the polymerase moves toward the 3Ј-end of genes, the level of Ser(P) 5 declines, whereas phosphorylation at Ser 2 (Ser(P)2 ) increases, recruiting nuclear factors responsible for elongation, termination, and 3Ј-end formation (3). The variable phosphorylation patterns within each heptad repeat, and distributions of these patterns across the full domain create a "CTD code" with a staggering potential complexity (4).In addition to phosphorylation, proline isomerization provides a second mechanism for regulating the association of CTD-binding partners (5). Due to its cyclic side chain, proline can adopt both cis and trans conformations about its peptide bond, creating distinct and interconvertible backbone structures with the cis isomer being energetically disfavored and therefore less populated (6). Each CTD heptad contains 2 proline residues, and both are preceded by serine residues that are critical targets of phosphorylation. Phosphorylation of Ser-Pro motifs in non-CTD peptides has been shown to modestly stabilize the cis form and decrease the rate of isomerization (7). A study with a Ser(P) 2 CTD peptide reported a cis population of Ͻ30% for the Ser(P) 2 -Pro 3 moti...

Background: Translesion synthesis in mammalian cells is achieved by sequential actions of insertion and extension polymerases. Results: We determined the Rev1-Pol -Pol complex structure and verified the binding interface with in vivo studies. Conclusion: Mammalian insertion and extension polymerases could cooperate within a megatranslesion polymerase complex nucleated by Rev1. Significance: The Rev1-Pol interface is a target for developing novel cancer therapeutics.

Compounds inhibiting LpxC in the lipid A biosynthetic pathway are promising leads for novel antibiotics against multidrug-resistant Gram-negative pathogens. We report the syntheses and structural and biochemical characterizations of LpxC inhibitors based on a diphenyl-diacetylene (1,4-diphenyl-1,3-butadiyne) threonylhydroxamate scaffold. These studies provide a molecular interpretation for the differential antibiotic activities of compounds with a substituted distal phenyl ring as well as the absolute stereochemical requirement at the C2, but not C3, position of the threonyl group.

Protein S-acylation is a reversible lipidic posttranslational modification where a fatty acid chain is covalently linked to cysteine residues by a thioester linkage. A family of integral membrane enzymes known as DHHC protein acyltransferases (DHHC-PATs) catalyze this reaction. With the rapid development of the techniques used for identifying lipidated proteins, the repertoire of S-acylated proteins continues to increase. This, in turn, highlights the important roles that S-acylation plays in human physiology and disease. Recently, the first molecular structures of DHHC-PATs were determined using X-ray crystallography. This review will comment on the insights gained on the molecular mechanism of S-acylation from these structures in combination with a wealth of biochemical data generated by researchers in the field.

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Carbon dioxide (CO 2 ) conversion technology has been estimated as a potentially practical solution for global warming problems although it still has some weaknesses such as cost and energy consumption. In this study, a combined steam reforming process with dry methane reforming process for the CO 2 treatment was investigated. Because the dry methane reforming process could generate synthesis gas from carbon dioxide, it could decrease the CO 2 emissions from the existing steam reforming process. Models for the steam reforming process and the combined process were developed and extended mitigation cost was suggested to evaluate CO 2 reduction of the overall process. The combined process could reduce net CO 2 emission by 67% compared with the reference steam reforming process, and the extended mitigation cost of the combined process ranged from 21 to 26.5 (US$/CO 2 ton) according to the change of the cost for CO 2 transportation.

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