scholarly journals Structural insights into vesicle amine transport-1 (VAT-1) as a member of the NADPH-dependent quinone oxidoreductase family

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sun-Yong Kim ◽  
Tomoyuki Mori ◽  
Min Fey Chek ◽  
Shunji Furuya ◽  
Ken Matsumoto ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Bound State ◽  
Dimensional Structure ◽  
Molecular Function ◽  
Quinone Oxidoreductase ◽  
Oxidoreductase Activity ◽  
Putative Active Site ◽  
Binding Cleft ◽  
Phospholipid Transport ◽  
Structural Insights

AbstractVesicle amine transport protein-1 (VAT-1) has been implicated in the regulation of vesicular transport, mitochondrial fusion, phospholipid transport and cell migration, and is a potential target of anticancer drugs. Little is known about the molecular function of VAT-1. The amino acid sequence indicates that VAT-1 belongs to the quinone oxidoreductase subfamily, suggesting that VAT-1 may possess enzymatic activity in unknown redox processes. To clarify the molecular function of VAT-1, we determined the three-dimensional structure of human VAT-1 in the free state at 2.3 Å resolution and found that VAT-1 forms a dimer with the conserved NADPH-binding cleft on each protomer. We also determined the structure of VAT-1 in the NADP-bound state at 2.6 Å resolution and found that NADP binds the binding cleft to create a putative active site with the nicotine ring. Substrate screening suggested that VAT-1 possesses oxidoreductase activity against quinones such as 1,2-naphthoquinone and 9,10-phenanthrenequinone.

Structure of Human Apolactoferrin at 2.0 Å Resolution. Refinement and Analysis of Ligand-Induced Conformational Change

1998 ◽  
Vol 54 (6) ◽  
pp. 1319-1335 ◽  
Author(s):  
Geoffrey B. Jameson ◽  
Bryan F. Anderson ◽  
Gillian E. Norris ◽  
David H. Thomas ◽  
Edward N. Baker
Keyword(s):  
Surface Area ◽  
Conformational Change ◽  
Crystal Packing ◽  
Three Dimensional ◽  
Chloride Ions ◽  
Dimensional Structure ◽  
Iron Binding ◽  
Data Set ◽  
Binding Cleft ◽  
Accessible Surface

The three-dimensional structure of a form of human apolactoferrin, in which one lobe (the N-lobe) has an open conformation and the other lobe (the C-lobe) is closed, has been refined at 2.0 Å resolution. The refinement, by restrained least-squares methods, used synchrotron radiation X-ray diffraction data combined with a lower resolution diffractometer data set. The final refined model (5346 protein atoms from residues 1–691, two Cl− ions and 363 water molecules) gives a crystallographic R factor of 0.201 (R free = 0.286) for all 51305 reflections in the resolution range 10.0–2.0 Å. The conformational change in the N-lobe, which opens up the binding cleft, involves a 54° rotation of the N2 domain relative to the N1 domain. This also results in a small reorientation of the two lobes relative to one another with a further ∼730 Å2 of surface area being buried as the N2 domain contacts the C-lobe and the inter-lobe helix. These new contacts also involve the C-terminal helix and provide a mechanism through which the conformational and iron-binding status of the N-lobe can be signalled to the C-lobe. Surface-area calculations indicate a fine balance between open and closed forms of lactoferrin, which both have essentially the same solvent-accessible surface. Chloride ions are bound in the anion-binding sites of both lobes, emphasizing the functional significance of these sites. The closed configuration of the C-lobe, attributed in part to weak stabilization by crystal packing interactions, has important implications for lactoferrin dynamics. It shows that a stable closed structure, essentially identical to that of the iron-bound form, can be formed in the absence of iron binding.

scholarly journals Structural Model for 12-Helix Transporters Belonging to the Major Facilitator Superfamily

2003 ◽  
Vol 185 (5) ◽  
pp. 1712-1718 ◽  
Author(s):  
Teruhisa Hirai ◽  
Jürgen A. W. Heymann ◽  
Peter C. Maloney ◽  
Sriram Subramaniam
Keyword(s):  
Structural Model ◽  
Structural Information ◽  
Three Dimensional ◽  
Spatial Arrangement ◽  
Bound State ◽  
Major Facilitator Superfamily ◽  
Dimensional Structure ◽  
Sequence Information ◽  
Major Facilitator ◽  
Related Proteins

ABSTRACT The major facilitator superfamily includes a large collection of evolutionarily related proteins that have been implicated in the transport of a variety of solutes and metabolites across the membranes of organisms ranging from bacteria to humans. We have recently reported the three-dimensional structure, at 6.5 Å resolution, of the oxalate transporter, OxlT, a representative member of this superfamily. In the oxalate-bound state, 12 helices surround a central cavity to form a remarkably symmetrical structure that displays a well-defined pseudo twofold axis perpendicular to the plane of the membrane as well as two less pronounced, mutually perpendicular pseudo twofold axes in the plane of the membrane. Here, we combined this structural information with sequence information from other members of this protein family to arrive at models for the arrangement of helices in this superfamily of transport proteins. Our analysis narrows down the number of helix arrangements from about a billion starting possibilities to a single probable model for the relative spatial arrangement for the 12 helices, consistent both with our structural findings and with the majority of previous biochemical studies on members of this superfamily.

Three-dimensional Structure of S. cerevisiae Phosphofructokinase: The ATP Bound State

2004 ◽  
Vol 10 (S02) ◽  
pp. 1506-1507
Author(s):  
Montserrat Barcena ◽  
Michael Radermacher ◽  
Jörg Bär ◽  
Gerhard Kopperschläger ◽  
Teresa Ruiz
Keyword(s):  
Three Dimensional ◽  
Bound State ◽  
Dimensional Structure ◽  
Three Dimensional Structure

Extended abstract of a paper presented at Microscopy and Microanalysis 2004 in Savannah, Georgia, USA, August 1–5, 2004.

scholarly journals Conformational Changes of Spo0F along the Phosphotransfer Pathway

2005 ◽  
Vol 187 (24) ◽  
pp. 8221-8227 ◽  
Author(s):  
Kottayil I. Varughese
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Conformational Changes ◽  
Solution Structure ◽  
Three Dimensional ◽  
Bound State ◽  
Dimensional Structure ◽  
Single Domain Protein ◽  
Secondary Messenger ◽  
Domain Protein ◽  
Apo State

ABSTRACT Spo0F is a secondary messenger in the sporulation phosphorelay, and its structure has been characterized crystallographically in the apo-state, in the metal-bound state, and in an interacting state with a phosphotransferase. Additionally, the solution structure of the molecule has been characterized by nuclear magnetic resonance techniques in the unliganded state and in complex with beryllofluoride. Spo0F is a single-domain protein with a well-defined three-dimensional structure, but it is capable of adapting to specific conformations for catching and releasing the phosphoryl moiety. This commentary deals with the conformational fluctuations of the molecule as it moves from an apo-state to a metal-coordinated state, to a phosphorylated state, and then to a phosphoryl-transferring state.

scholarly journals Three-Dimensional Structure of AAA ATPase Vps4: Advancing Structural Insights into the Mechanisms of Endosomal Sorting and Enveloped Virus Budding

Structure ◽  
2009 ◽  
Vol 17 (3) ◽  
pp. 427-437 ◽  
Author(s):  
Michael John Landsberg ◽  
Parimala Rao Vajjhala ◽  
Rosalba Rothnagel ◽  
Alan Leslie Munn ◽  
Ben Hankamer
Keyword(s):  
Three Dimensional ◽  
Dimensional Structure ◽  
Virus Budding ◽  
Three Dimensional Structure ◽  
Endosomal Sorting ◽  
Aaa Atpase ◽  
Enveloped Virus ◽  
Structural Insights

scholarly journals Lis1 regulates dynein by sterically blocking its mechanochemical cycle

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Katerina Toropova ◽  
Sirui Zou ◽  
Anthony J Roberts ◽  
William B Redwine ◽  
Brian S Goodman ◽  
...  
Keyword(s):  
Single Molecule ◽  
Intracellular Transport ◽  
Three Dimensional ◽  
Bound State ◽  
Dimensional Structure ◽  
Dimensional Electron ◽  
In Vivo Assays ◽  
Mechanical Element ◽  
Mechanochemical Cycle

Regulation of cytoplasmic dynein's motor activity is essential for diverse eukaryotic functions, including cell division, intracellular transport, and brain development. The dynein regulator Lis1 is known to keep dynein bound to microtubules; however, how this is accomplished mechanistically remains unknown. We have used three-dimensional electron microscopy, single-molecule imaging, biochemistry, and in vivo assays to help establish this mechanism. The three-dimensional structure of the dynein–Lis1 complex shows that binding of Lis1 to dynein's AAA+ ring sterically prevents dynein's main mechanical element, the ‘linker’, from completing its normal conformational cycle. Single-molecule experiments show that eliminating this block by shortening the linker to a point where it can physically bypass Lis1 renders single dynein motors insensitive to regulation by Lis1. Our data reveal that Lis1 keeps dynein in a persistent microtubule-bound state by directly blocking the progression of its mechanochemical cycle.

scholarly journals Three-dimensional Structure and Enzymatic Function of Proapoptotic Human p53-inducible Quinone Oxidoreductase PIG3

2009 ◽  
Vol 284 (25) ◽  
pp. 17194-17205 ◽  
Author(s):  
Sergio Porté ◽  
Eva Valencia ◽  
Evgenia A. Yakovtseva ◽  
Emma Borràs ◽  
Naeem Shafqat ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Dimensional Structure ◽  
Quinone Oxidoreductase ◽  
Three Dimensional Structure ◽  
Enzymatic Function

scholarly journals Importance of Homology Modeling for Predicting the Structures of GPCRs

2020 ◽  
Author(s):  
Ananthasri Sailapathi ◽  
Seshan Gunalan ◽  
Kanagasabai Somarathinam ◽  
Gugan Kothandan ◽  
Diwakar Kumar
Keyword(s):  
Structural Analysis ◽  
Homology Modeling ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Ligand Interaction ◽  
Receptor Ligand ◽  
In Silico Models ◽  
Structural Insights ◽  
Multiple Template ◽  
Important Drug

Homology modeling is one of the key discoveries that led to a rapid paradigm shift in the field of computational biology. Homology modeling obtains the three dimensional structure of a target protein based on the similarity between template and target sequences and this technique proves to be efficient when it comes to studying membrane proteins that are hard to crystallize like GPCR as it provides a higher degree of understanding of receptor-ligand interaction. We get profound insights on structurally unsolved, yet clinically important drug targeting proteins through single or multiple template modeling. The advantages of homology modeling studies are often used to overcome various problems in crystallizing GPCR proteins that are involved in major disease-related pathways, thus paving way to more structural insights via in silico models when there is a lack of experimentally solved structures. Owing to their pharmaceutical significance, structural analysis of various GPCR proteins using techniques like homology modeling is of utmost importance.

scholarly journals Mapping Mutations in Proteins of SARS CoV-2 Indian Isolates on to the Three-Dimensional Structures

2020 ◽  
Author(s):  
Kunchur Guruprasad
Keyword(s):  
Rna Polymerase ◽  
Binding Sites ◽  
Three Dimensional ◽  
Data Bank ◽  
Drug Binding ◽  
Dimensional Structure ◽  
Rna Dependent Rna Polymerase ◽  
Indian Isolates ◽  
Drug Binding Sites ◽  
Structural Insights

<p>The amino acid residue mutations observed in SARS CoV-2 RNA dependent RNA polymerase, helicase, endoRNAse and spike proteins from Indian isolates, relative to the reference SARS CoV-2 proteins from the Wuhan Hu-1 isolate, were mapped onto the protein three-dimensional structure templates available in the Protein Data Bank.<b> </b>The secondary structure conformations corresponding to the mutations, their locations and proximity to functionally important residues in these proteins and to the drug binding sites in RNA dependent RNA polymerase and endoRNAse targets were analysed. Our analyses provide structural insights into the mutations in these SARS CoV-2 proteins.</p>

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