Structural Basis of Redox Signaling in Photosynthesis: Structure and Function of Ferredoxin:thioredoxin Reductase and Target Enzymes

AbstractObjectiveWe identify the impacts of structural differences on functionality of EG3_S2 endoglucanase enzyme with MD studies. The results of previous experimental studies have been explained in details with computational approach. The objective of this study is to explain the functional differences between shuffled enzyme (EG3_S2) and its native counterpart (EG3_nat) from Trichoderma reseei, via Molecular Dynamics approach.Materials and methodsFor this purpose, we performed MD simulations along 30 ns at three different reaction temperatures collected as NpT ensemble, and then monitored the backbone motion, flexibilities of residues, and intramolecular interactions of EG3_S2 and EG3_nat enzymes.ResultsAccording to MD results, we conclude that EG3_S2 and EG3_nat enzymes have unique RMSD patterns, e.g. RMSD pattern of EG3_S2 is more dynamic than that of EG3_nat at all temperatures. In addition to this dynamicity, EG3_S2 establishes more salt bridge interactions than EG3_nat.ConclusionBy taking these results into an account with the preservation of catalytic Glu residues in a proper manner, we explain the structural basis of differences between shuffled and native enzyme via molecular dynamic studies.

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A replicative and synthetic chromosomal unit-the modern concept of the chromomere

Proceedings of the Royal Society of London Series B Biological Sciences ◽

10.1098/rspb.1966.0030 ◽

1966 ◽

Vol 164 (995) ◽

pp. 279-289 ◽

Cited By ~ 57

Keyword(s):

Molecular Level ◽

Structure And Function ◽

Structural Basis ◽

Modern Concept ◽

Chromosomal Structure ◽

New Approaches ◽

Combined Use ◽

And Function

present-day discussions on chromosomal structure and function the old term chromomere’ (Fol 1891) is seldom mentioned and it may be debated whether at is still desirable to use such a term. Conventionally it describes the bead-like concentrations of chromatin linearly arranged along the chromosomal thread, without implications as to the structural basis of such a discontinuity. Two alternative interpretations of the chromomeric organization of the chromosome have been suggested, one in which the chromomeres were regarded as definite chromosomal bodies, different from the interchromomeric regions of the chromosome, and one which considered the chromomeres as structures resulting only from the local coiling of a continuous chromosomal thread. Neither the chromomere hypothesis (Belling 1928; Bridges 1935; Pontecorvo 1944) nor the chromonema hypothesis (Ris 1945) has been finally and universally accepted. This is because the morphological and cytogenetical evidence previously available was insufficient to extend our knowledge of chromosomal structure down to the molecular level. New approaches in this direction have recently been made by the combined use of cytological, autoradiographic and photometric methods. They draw new attention to the chromomere.

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Computational Modeling of Claudin Structure and Function

International Journal of Molecular Sciences ◽

10.3390/ijms21030742 ◽

2020 ◽

Vol 21 (3) ◽

pp. 742 ◽

Cited By ~ 2

Author(s):

Shadi Fuladi ◽

Ridaka-Wal Jannat ◽

Le Shen ◽

Christopher R. Weber ◽

Fatemeh Khalili-Araghi

Keyword(s):

Small Molecules ◽

Tight Junctions ◽

Barrier Function ◽

Functional Model ◽

Structure And Function ◽

Structural Basis ◽

Crystallographic Structure ◽

Epithelial Barrier Function ◽

Transport Of Ions ◽

And Function

Tight junctions form a barrier to control passive transport of ions and small molecules across epithelia and endothelia. In addition to forming a barrier, some of claudins control transport properties of tight junctions by forming charge- and size-selective ion channels. It has been suggested claudin monomers can form or incorporate into tight junction strands to form channels. Resolving the crystallographic structure of several claudins in recent years has provided an opportunity to examine structural basis of claudins in tight junctions. Computational and theoretical modeling relying on atomic description of the pore have contributed significantly to our understanding of claudin pores and paracellular transport. In this paper, we review recent computational and mathematical modeling of claudin barrier function. We focus on dynamic modeling of global epithelial barrier function as a function of claudin pores and molecular dynamics studies of claudins leading to a functional model of claudin channels.

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LimF is a versatile prenyltransferase catalyzing histidine-C-geranylation on diverse nonnatural substrates

10.26434/chemrxiv-2021-v70zf ◽

2021 ◽

Author(s):

Yuchen Zhang ◽

Keisuke Hamada ◽

Dinh Thanh Nguyen ◽

Sumika Inoue ◽

Masayuki Satake ◽

...

Keyword(s):

Crystallographic Analysis ◽

Structure And Function ◽

Bioactive Molecules ◽

Structural Basis ◽

Peptide Substrate ◽

Site Specific ◽

Native Peptide ◽

Wide Range ◽

Secondary Function ◽

And Function

Prenylation plays an important role in diversifying structure and function of secondary metabolites. Although several cyanobactin prenyltransferases have been characterized, their modes of action are mainly limited to the modification of electron-rich hetero atoms. Here we report a unique prenyltransferase originating from Limnothrix sp. CACIAM 69d, referred to as LimF, which catalyzes an unprecedented His-C-geranylation. Interestingly, LimF executes the geranylation on not only its native peptide substrate but also a wide range of exotic peptides, including thioether-closed macrocycles. We have also serendipitously uncovered an ability of Tyr-O-geranylation as the secondary function of LimF, indicating it is an unusual bifunctional prenyltransferase. Crystallographic analysis of LimF complexed with a pentapeptide substrate and a prenyl donor analog provides structural basis for its unique His recognition and its bifunctionality. Lastly, we show the LimF’s prenylation ability on various bioactive molecules containing an imidazole group, highlighting its potential as a versatile biocatalyst for site-specific geranylation.

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Thomas Arthur Steitz. 23 August 1940—9 October 2018

Biographical Memoirs of Fellows of the Royal Society ◽

10.1098/rsbm.2021.0029 ◽

2021 ◽

Author(s):

V. Ramakrishnan ◽

Richard Henderson

Keyword(s):

Nobel Prize ◽

Genetic Information ◽

Metabolic Enzymes ◽

Structure And Function ◽

Structural Basis ◽

Biological Macromolecules ◽

Research Career ◽

And Function

Thomas A. Steitz was among the foremost of the generation that was responsible for an explosion in our understanding of the structure and function of biological macromolecules. His research career was one of sustained excellence over six decades, and spanned the range from determining the structures of important metabolic enzymes to understanding the structural basis of how genetic information residing in our DNA is used to make the proteins they encode. This latter effort culminated in the structure of the ribosome, for which he shared the Nobel Prize in Chemistry in 2009.

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Structure-Function and Industrial Relevance of Bacterial Aminopeptidase P

Catalysts ◽

10.3390/catal11101157 ◽

2021 ◽

Vol 11 (10) ◽

pp. 1157

Author(s):

Muhamad Nadzmi Omar ◽

Raja Noor Zaliha Raja Abd Rahman ◽

Noor Dina Muhd Noor ◽

Wahhida Latip ◽

Victor Feizal Knight ◽

...

Keyword(s):

Metal Ion ◽

Catalytic Mechanism ◽

Structure And Function ◽

Structural Basis ◽

Methionine Aminopeptidase ◽

Terminal Amino ◽

Aminopeptidase P ◽

And Function ◽

Pita Bread ◽

Industrial Relevance

Aminopeptidase P (APPro, E.C 3.4.11.9) cleaves N-terminal amino acids from peptides and proteins where the penultimate residue is proline. This metal-ion-dependent enzyme shares a similar fold, catalytic mechanism, and substrate specificity with methionine aminopeptidase and prolidase. It adopts a canonical pita bread fold that serves as a structural basis for the metal-dependent catalysis and assembles as a tetramer in crystals. Similar to other metalloaminopeptidase, APPro requires metal ions for its maximal enzymatic activity, with manganese being the most preferred cation. Microbial aminopeptidase possesses unique characteristics compared with aminopeptidase from other sources, making it a great industrial enzyme for various applications. This review provides a summary of recent progress in the study of the structure and function of aminopeptidase P and describes its various applications in different industries as well as its significance in the environment.

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Biotransformation of Explosives by the Old Yellow Enzyme Family of Flavoproteins

Applied and Environmental Microbiology ◽

10.1128/aem.70.6.3566-3574.2004 ◽

2004 ◽

Vol 70 (6) ◽

pp. 3566-3574 ◽

Cited By ~ 138

Author(s):

Richard E. Williams ◽

Deborah A. Rathbone ◽

Nigel S. Scrutton ◽

Neil C. Bruce

Keyword(s):

Transformation Products ◽

Structure And Function ◽

Bacterial Degradation ◽

Structural Basis ◽

Old Yellow Enzyme ◽

Nitrate Ester ◽

Initial Reduction ◽

Nitroaromatic Explosive ◽

And Function

ABSTRACT Several independent studies of bacterial degradation of nitrate ester explosives have demonstrated the involvement of flavin-dependent oxidoreductases related to the old yellow enzyme (OYE) of yeast. Some of these enzymes also transform the nitroaromatic explosive 2,4,6-trinitrotoluene (TNT). In this work, catalytic capabilities of five members of the OYE family were compared, with a view to correlating structure and function. The activity profiles of the five enzymes differed substantially; no one compound proved to be a good substrate for all five enzymes. TNT is reduced, albeit slowly, by all five enzymes. The nature of the transformation products differed, with three of the five enzymes yielding products indicative of reduction of the aromatic ring. Our findings suggest two distinct pathways of TNT transformation, with the initial reduction of TNT being the key point of difference between the enzymes. Characterization of an active site mutant of one of the enzymes suggests a structural basis for this difference.

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2SDA-01 Structural basis of chromatin dynamics regulated by histone variants(2SDA Studies of dynamic chromatin structure and function to understand fundamentals of life,Symposium,The 52nd Annual Meeting of the Biophysical Society of Japan(BSJ2014))

Seibutsu Butsuri ◽

10.2142/biophys.54.s127_6 ◽

2014 ◽

Vol 54 (supplement1-2) ◽

pp. S127

Author(s):

Hitoshi Kurumizaka

Keyword(s):

Annual Meeting ◽

Chromatin Structure ◽

Histone Variants ◽

Structure And Function ◽

Structural Basis ◽

Chromatin Dynamics ◽

Biophysical Society ◽

And Function

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How my Experiences at the MRC-LMB led to the Structure of the Ribosome

Acta Crystallographica Section A Foundations and Advances ◽

10.1107/s2053273314090640 ◽

2014 ◽

Vol 70 (a1) ◽

pp. C935-C935

Author(s):

Thomas Steitz

Keyword(s):

Data Collection ◽

Molecular Biology ◽

Atomic Structure ◽

Structure And Function ◽

Structural Basis ◽

Asymmetric Unit ◽

Carboxypeptidase A ◽

Central Dogma ◽

And Function ◽

Resolution Data

Max Perutz's Dunham Lectures at Harvard in 1963, in which he showed the first atomic structure of a protein (myoglobin) that anyone in the room had ever seen, led to my working on the structure of carboxypeptidase A (CPA) (in the Lipscomb lab) before going to the MRC LMB in Cambridge. "Rapid" data collection on CPA in the mid-1960s was 5,000 reflections in a week, and now obtaining 2.7 Å resolution data on crystals with two 70S ribosomes in the asymmetric unit takes 5 minutes. Importantly, the LMB promoted creative and novel science because of its cooperative, interactive atmosphere where everyone interacted in the hall or over coffee, lunch or tea. This influenced how I have carried out science over the subsequent years. In the canteen, Crick, Brenner, Perutz, etc., would be interacting and talking with postdocs and students about asking important questions and solving scientific problems. It was a great place to learn, develop and use the most advanced methods in protein crystallography and apply them to explore the most interesting and significant questions in molecular biology. The importance of integrating structure and function in our research goals was made clear. My interactions in the Cambridge LMB led me to pursue the structural basis for understanding Crick's Central Dogma of Molecular Biology – DNA makes DNA makes RNA makes proteins. This resulted in our ultimately determining the structures of the ribosome and its various complexes.

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Structure and function of crocodilian hemoglobins and allosteric regulation by chloride, ATP, and CO2

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00342.2019 ◽

2020 ◽

Vol 318 (3) ◽

pp. R657-R667 ◽

Cited By ~ 3

Author(s):

Angela Fago ◽

Chandrasekhar Natarajan ◽

Martín Pettinati ◽

Federico G. Hoffmann ◽

Tobias Wang ◽

...

Keyword(s):

Molecular Mechanisms ◽

Structural Information ◽

Allosteric Regulation ◽

Structure And Function ◽

Chloride Ions ◽

Amino Acid Sequences ◽

Regulatory Control ◽

Structural Basis ◽

Independent Effect ◽

And Function

Hemoglobins (Hbs) of crocodilians are reportedly characterized by unique mechanisms of allosteric regulatory control, but there are conflicting reports regarding the importance of different effectors, such as chloride ions, organic phosphates, and CO2. Progress in understanding the unusual properties of crocodilian Hbs has also been hindered by a dearth of structural information. Here, we present the first comparative analysis of blood properties and Hb structure and function in a phylogenetically diverse set of crocodilian species. We examine mechanisms of allosteric regulation in the Hbs of 13 crocodilian species belonging to the families Crocodylidae and Alligatoridae. We also report new amino acid sequences for the α- and β-globins of these taxa, which, in combination with structural analyses, provide insights into molecular mechanisms of allosteric regulation. All crocodilian Hbs exhibited a remarkably strong sensitivity to CO2, which would permit effective O2 unloading to tissues in response to an increase in metabolism during intense activity and diving. Although the Hbs of all crocodilians exhibit similar intrinsic O2-affinities, there is considerable variation in sensitivity to Cl− ions and ATP, which appears to be at least partly attributable to variation in the extent of NH2-terminal acetylation. Whereas chloride appears to be a potent allosteric effector of all crocodile Hbs, ATP has a strong, chloride-independent effect on Hb-O2 affinity only in caimans. Modeling suggests that allosteric ATP binding has a somewhat different structural basis in crocodilian and mammalian Hbs.

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