mmView: a web-based viewer of the mmCIF format

<p>Abstract</p> <p>Background</p> <p>Structural biomolecular data are commonly stored in the PDB format. The PDB format is widely supported by software vendors because of its simplicity and readability. However, the PDB format cannot fully address many informatics challenges related to the growing amount of structural data. To overcome the limitations of the PDB format, a new textual format mmCIF was released in June 1997 in its version 1.0. mmCIF provides extra information which has the advantage of being in a computer readable form. However, this advantage becomes a disadvantage if a human must read and understand the stored data. While software tools exist to help to prepare mmCIF files, the number of available systems simplifying the comprehension and interpretation of the mmCIF files is limited.</p> <p>Findings</p> <p>In this paper we present mmView - a cross-platform web-based application that allows to explore comfortably the structural data of biomacromolecules stored in the mmCIF format. The mmCIF categories can be easily browsed in a tree-like structure, and the corresponding data are presented in a well arranged tabular form. The application also allows to display and investigate biomolecular structures via an integrated Java application Jmol.</p> <p>Conclusions</p> <p>The mmView software system is primarily intended for educational purposes, but it can also serve as a useful research tool. The mmView application is offered in two flavors: as an open-source stand-alone application (available from <url>http://sourceforge.net/projects/mmview</url>) that can be installed on the user's computer, and as a publicly available web server.</p

Nonpeptidal P-2 ligands for HIV protease inhibitors: Structure-based design, synthesis, and biological evaluation

Design and synthesis of nonpeptidal bis-tetrahydrofuran ligands based upon the X-ray crystal structure of the HIV-1 protease-inhibitor complex 1 led to replacement of two amide bonds and a 10 pi-aromatic system of Ro 31-8959 class of HIV protease inhibitors. Detailed structure-activity studies have now established that the position of ring oxygens, ring size, and stereochemistry are all crucial to potency. Of particular interest, compound 49 with (3S,3aS,6aS)-bis-Thf is the most potent inhibitor (IC50 value 1.8 +/- 0.2 nM; CIC95 value 46 +/- 4 nM) in this series. The X-ray structure of protein-inhibitor complex 49 has provided insight into the ligand-binding site interactions. As it turned out, both oxygens in the bis-Thf ligands are involved in hydrogen-bonding interactions with Asp 29 and Asp 30 NH present in the S-2 subsite of HIV-1 protease. Stereoselective routes have been developed to obtain these novel ligands in optically pure form

Ice-binding structure and mechanism of an antifreeze protein from winter flounder

Antifreeze proteins provide fish with protection against the freezing effect of polar environments by binding to ice surfaces and inhibiting growth of ice crystals. We present the X-ray crystal structure at 1.5 Å resolution of a lone a-helical antifreeze protein from winter flounder, which provides a detailed look at its ice-binding features. These consist of four repeated ice-binding motifs, the side chains of which are inherently rigid or restrained by pairwise side-chain interactions to form a flat binding surface. Elaborate amino- and carboxy-terminal cap structures are also present, which explain the protein's rich a-helical content in solution. We propose an ice-binding model that accounts for the binding specificity of the antifreeze protein along the axes of the {2021} ice planes

Allosteric Transition Intermediates Modeled By Cross-linked Hemoglobins

THE structural end-points of haemoglobin's transition from its low-oxygen-affinity (T) to high-oxygen-affinity CR) state, have been well established by X-ray crystallography(1-7), but short-lived intermediates have proved less amenable to X-ray studies, Here we use chemical crosslinking to fix these intermediates for structural characterization. We describe the X-ray structures of three haemoglobins, alpha(2) beta(1)S(82)beta, alpha(2) beta(1)Tm(82)beta and alpha(2) beta(1,82)Tm(82)beta, which were crosslinked between the amino groups of residues beta Val1 and beta Lys82 by 3,3'-stilbenedicarboxylic acid (S) or trimesic acid (Tm) while in the deoxy state, and saturated with carbon monoxide before crystallization. alpha(2) beta(1)S(82)beta, which has almost normal oxygen affinity, is completely in the R-state conformation; however, alpha(2) beta(1)Tm(82)beta and alpha(2) beta(1,82)Tm(82)beta, both of which have low oxygen affinity, have been prevented from completing their transition into the R state and display many features of a transitional intermediate, These haemoglobins therefore represent a snapshot of the nascent R state.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62708/1/375084a0.pd

Crystal structure of Thermus aquaticus DNA polymerase

The DNA polymerase from Thermus aquaticus (Taq polymerase), famous for its use in the polymerase chain reaction, is homologous to Escherichia coli DNA polymerase I (pol I). Like pol I, Taq polymerase has a domain at its amino terminus (residues 1-290) that has 5' nuclease activity and a domain at its carboxy terminus that catalyses the polymerase reaction. Unlike pol I, the intervening domain in Tag polymerase has lost the editing 3'-5' exonuclease activity. Although the structure of the Klenow fragment of pol I has proved more elusive. The structure of Taq polymerase determined here at 2.4 ? resolution shows that the structures of the polymerase domains of the thermostable enzyme and of the Klenow fragment are nearly identical, whereas the catalytically critical carboxylate residues that bind two metal ions are missing from the remnants of the 3'-5'-exonuclease active site of Taq polymerase. The first view of the 5' nuclease domain, responsible for excising the Okazaki RNA in lagging-strand DNA replication, shows a cluster of conserved divalent metal-ion-binding carboxylates at the bottom of a cleft. The location of this 5'-nuclease active site some 70 ? from the polymerase active site in this crystal form highlights the unanswered question of how this domain works in concert with the polymerase domain to produce a duplex DNA product that contains only a nick.ope