Analysis of domain motions in large proteins

Hinsen, Konrad; Thomas, Aline; Field, Martin J.

doi:10.1002/(sici)1097-0134(19990215)34:3<369::aid-prot9>3.3.co;2-6

Cited by 110 publications

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“…Normal Mode Analysis (NMA) of ⌬I139M FAC1 Dimer-The dynamical domains in the ⌬I139M FAC1 dimer were determined using NMA (31) in the Molecular Modeling ToolKit (32). A deformation measure was calculated for the carbon ␣ (C␣) atom in each residue followed by normal mode calculations.…”

Section: Crystallization and Structure Determination Of ⌬I139m Fac1 Rmentioning

confidence: 99%

Membrane Association, Mechanism of Action, and Structure of Arabidopsis Embryonic Factor 1 (FAC1)

Han

Bingman

Mahnke

et al. 2006

Journal of Biological Chemistry

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Embryonic factor 1 (FAC1) is one of the earliest expressed plant genes and encodes an AMP deaminase (AMPD), which is also an identified herbicide target. This report identifies an N-terminal transmembrane domain in Arabidopsis FAC1, explores subcellular fractionation, and presents a 3.3-Å globular catalytic domain x-ray crystal structure with a bound herbicide-based transition state inhibitor that provides the first glimpse of a complete AMPD active site. FAC1 contains an (␣/␤) 8 -barrel characterized by loops in place of strands 5 and 6 that places it in a small subset of the amidohydrolase superfamily with imperfect folds. Unlike tetrameric animal orthologs, FAC1 is a dimer and each subunit contains an exposed Walker A motif that may be involved in the dramatic combined K m (25-80-fold lower) and V max (5-6-fold higher) activation by ATP. Normal mode analysis predicts a hinge motion that flattens basic surfaces on each monomer that flank the dimer interface, which suggests a reversible association between the FAC1 globular catalytic domain and intracellular membranes, with N-terminal transmembrane and disordered linker regions serving as the anchor and attachment to the globular catalytic domain, respectively.Embryonic factor 1 (FAC1) 5 was recently identified as one of the earliest expressed plant genes and is essential for the zygote to embryo transition in Arabidopsis thaliana (1). The zygote-lethal phenotype is characterized by developmental arrest at the 8 -16-cell stage and mutant embryo shriveling 2-3 days after fertilization. The Arabidopsis FAC1 locus encodes an AMP deaminase (AMPD; EC 3.5.4.6), which is a eukaryotic enzyme that catalyzes the hydrolytic deamination of AMP to IMP. AMPD has also been identified as the intracellular target for a class of herbicides that are produced by fungal pathogens. Carbocyclic coformycin was initially discovered in Saccharothrix (2), and plant cells can take up this diffusible nucleoside and 5Ј-phosphorylate it to produce a potent transition state inhibitor of AMPD (3). Exposure to carbocyclic coformycin results in cessation of seedling growth, followed by paling and necrosis at the apical meristem (3). Coformycin, a structurally related compound produced by a number of microbes (4, 5), also has herbicidal properties (5). Although the intracellular metabolism of this compound in plants has not been examined, its mode of action is presumably similar because coformycin 5Ј-phosphate is a transition state inhibitor of rabbit muscle AMPD (6). Both herbicides are inhibitors of mammalian adenosine deaminase (ADA) (3, 6), but the lack of this enzyme in plants (3, 7-9) supports the argument that AMPD is the intracellular target for their nucleotide derivatives. Taken together, these observations suggest that AMPD is essential throughout the plant life cycle. However, the underlying basis for lethality of a FAC1 null phenotype and for herbicidal toxicity related to the catalytic inhibition of this enzyme is not known.AMPD catalyzes the initial step in adenine to guanine ribon...

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Section: Crystallization and Structure Determination Of ⌬I139m Fac1 Rmentioning

confidence: 99%

Membrane Association, Mechanism of Action, and Structure of Arabidopsis Embryonic Factor 1 (FAC1)

Han

Bingman

Mahnke

et al. 2006

Journal of Biological Chemistry

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“…In this paper, we propose a mathematical definition for the concept of rigid domain that has appeared in the literature [14,22,15,10,20] in mostly imprecise form. Using our definition, we present an efficient approximation algorithm for finding the rigid domains of a protein, given two conformations of the protein.…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…These include the pioneering work by Gerstein et al [8], MolMovDB [7,14,5] by Gerstein et al, HingeFind [22] by Wrigger et al, DomainFinder [15,16] by Hinsen, DynDom [10,11,12,13] by Hayward et al,and [20] by Nichols et al Most of these papers consider more general problems than identifying rigid domains; for example, they including the one by Nichols et al More specifically, the descriptions of rigid domains in these papers include the following two characteristics: (1) the residues in a rigid domain move relatively rigidly; in other words, the residues in a domain move with similar rigid motions. (2) The distances of residues in a rigid domain are approximately conserved, i.e.…”

Section: Introductionmentioning

confidence: 99%

“…The identification of rigid domains is therefore useful in understanding the structure-function relationship of proteins. Many algorithms, including [14,22,15,10,20], have been developed to identify rigid domains.In this paper, we complement these works by proposing a mathematical definition of a rigid domain. We argue that our definition more accurately captures the intuitive notion of rigid domain in the previous work, than the quantitative definition of a rigid domain introduced by Nichols et al [20].…”

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An Algorithmic Approach to the Identification of Rigid Domains in Proteins

Choi

Goyal

2007

Algorithmica

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Many proteins undergo conformational changes to perform their functions. A simple mechanism of conformational change in proteins is a rigid domain motion, in which two parts of a structure move rigidly with respect to each other. The identification of rigid domains is therefore useful in understanding the structure-function relationship of proteins. Many algorithms, including [14,22,15,10,20], have been developed to identify rigid domains.In this paper, we complement these works by proposing a mathematical definition of a rigid domain. We argue that our definition more accurately captures the intuitive notion of rigid domain in the previous work, than the quantitative definition of a rigid domain introduced by Nichols et al. [20]. Furthermore, our definition admits a practical approximation algorithm. We can prove theoretical guarantee on the quality of the output of our algorithm. We implement a randomized version of our algorithm, and demonstrate its effectiveness on several known protein complexes.

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The molecular modeling toolkit: A new approach to molecular simulations

2000

Self Cite

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The Molecular Modeling Toolkit is a library that implements common molecular simulation techniques, with an emphasis on biomolecular simulations. It uses modern software engineering techniques (object‐oriented design, a high‐level language) to overcome limitations associated with the large monolithic simulation programs that are commonly used for biomolecules. Its principal advantages are (1) easy extension and combination with other libraries due to modular library design; (2) a single high‐level general‐purpose programming language (Python) is used for library implementation as well as for application scripts; (3) use of documented and machine‐independent formats for all data files; and (4) interfaces to other simulation and visualization programs. © 2000 John Wiley & Sons, Inc. J Comput Chem 21: 79–85, 2000

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Analysis of domain motions in large proteins

Cited by 110 publications

References 0 publications

Membrane Association, Mechanism of Action, and Structure of Arabidopsis Embryonic Factor 1 (FAC1)

Membrane Association, Mechanism of Action, and Structure of Arabidopsis Embryonic Factor 1 (FAC1)

An Algorithmic Approach to the Identification of Rigid Domains in Proteins

The molecular modeling toolkit: A new approach to molecular simulations

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