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1. |
A metal‐mediated hydride shift mechanism for xylose isomerase based on the 1.6 ÅStreptomycs rubiginosusstructure with xylitol andD‐xylose |
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Proteins: Structure, Function, and Bioinformatics,
Volume 9,
Issue 3,
1991,
Page 153-173
Marc Whitlow,
Andrew J. Howard,
Barry C. Finzel,
Thomas L. Poulos,
Evon Winborne,
Gary L. Gilliland,
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摘要:
AbstractThe crystal structure of recombinantStreptomyces rubiginousD‐xylose isomerase (D‐xylose keto‐isomerase, EC 5.3.1.5) solved by the multiple isomorphous replacement technique has been refined toR= 0.16 at 1.64 Å resolution. As observed in an earlier study at 4.0 Å (Carrell et al., J. Biol. Chem. 259: 3230–3236, 1984), xylose isomerase is a tetramer composed of four identical subunits. The monomer consists of an eight‐stranded parallel β‐barrel surrounded by eight helices with an extended C‐terminal tail that provides extensive contacts with a neighboring monomer. The active site pocket is defined by an opening in the barrel whose entrance is lined with hydrophobic residues while the bottom of the pocket consists mainly of glutamate, aspartate, and histidine residues coordinated to two manganese ions.The structures of the enzyme in the presence of MnCl2, the inhibitor xylitol, and the substrateD‐xylose in the presence and absence of MnCl2have also been refined toR= 0.14 at 1.60 Å,R= 0.15 at 1.71 Å,R= 0.15 at 1.60 Å, andR= 0.14 at 1.60 Å, respectively. Both the ring oxygen of the cyclic α‐D‐xylose and its C1 hydroxyl are within hydrogen bonding distance of NE2 of His‐54 in the structure crystallized in the presence ofD‐xylose. Both the inhibitor, xylitol, and the extended form of the substrate,D‐xylose, bind such that the C2 and C4 OH groups interact with one of the two divalent cations found in the active site and the C1 OH with the other cation. The remainder of the OH groups hydrogen bond with neighboring amino acid side chains.A detailed mechanism forD‐xylose isomerase is proposed. Upon binding of cyclic α‐D‐xylose to xylose isomerase, His‐54 acts as the catalytic base in a ring opening reaction. The ring opening step is followed by binding ofD‐xylose, in volving two divalent cations, in an extended conformation. The isomerization ofD‐xylose toD‐xylulose involves a metal‐mediated 1,2‐hydride shift. The final step in the mechanism is a ring closure to produce α‐D‐xylulose. The ring closing is the reverse of the ring opening step.This mechanism accounts for the majority of xylose iomerase's biochemical properties, in cluding (1) the lack of solvent exchange between the 2‐position ofD‐xylose and the 1‐pro‐Rposition ofD‐xylulose, (2) the chemical modification of histidine and lysine, (3) the pH vs. activity profile
ISSN:0887-3585
DOI:10.1002/prot.340090302
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1991
数据来源: WILEY
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2. |
The three‐dimensional structure of glutathione reductase fromEscherichia coliat 3.0 Å resolution |
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Proteins: Structure, Function, and Bioinformatics,
Volume 9,
Issue 3,
1991,
Page 174-179
Ulrich Ermler,
Georg E. Schulz,
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摘要:
AbstractThe structure of glutathione reductase fromEscherichia colihas been solved at 3 Å resolution using multiple isomorphous replacement, solvent flattening, and molecular replacement on the basis of the homologous (53% identical residues) and structurally well‐established human enzyme. The structures of both enzyme species agree with each other in a global way; there is no domain rearrangement. In detail, clear structural differences can be observed. The structure analysis of theE. colienzyme was tackled in order to understand sitedirected mutants, the most spectacular of which changed the cofactor specificity of this enzyme from NADP to NAD (Scrutton et al., 1990, Nature 343:38
ISSN:0887-3585
DOI:10.1002/prot.340090303
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1991
数据来源: WILEY
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3. |
A workbench for multiple alignment construction and analysis |
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Proteins: Structure, Function, and Bioinformatics,
Volume 9,
Issue 3,
1991,
Page 180-190
Gregory D. Schuler,
Stephen F. Altschul,
David J. Lipman,
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摘要:
AbstractMultiple sequence alignment can be a useful technique for studying molecular evolution, as well as for analyzing relationships between structure or function and primary sequence. We have developed for this purpose an interactive program, MACAW (Multiple Alignment Construction and Analysis Workbench), that allows the user to construct multiple alignments by locating, analyzing, editing, and combining “blocks” of aligned sequence segments. MACAW incorporates several novel features. (1) Regions of local similarity are located by a new search algorithm that avoids many of the limitations of previous techniques. (2) The statistical significance of blocks of similarity is evaluted using a recently developed mathematical theory. (3) Candidate blocks may be evaluated for potential inclusion in a multiple alignment using a variety of visualization tools. (4) A user interface permits each blocks to be edited by moving its boundaries or by eliminating particular segments, and blocks may be linked to form a composite multiple alignment. No completely automatic program is likely to deal effectively with all the complexities of the multiple alignment problem; by combining a powerful similarity search algorithm with flexible editing, analysis and display tools, MACAW allows the alignment strategy to be tailored to the problem at h
ISSN:0887-3585
DOI:10.1002/prot.340090304
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1991
数据来源: WILEY
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4. |
Comparative modeling of mammalian aspartate transcarbamylase |
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Proteins: Structure, Function, and Bioinformatics,
Volume 9,
Issue 3,
1991,
Page 191-206
Joshua L. Scully,
David R. Evans,
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摘要:
AbstractMammalian aspartate transcarbamylase (ATCase) is part of a 243 kDa multidomain polypeptide, called CAD, that catalyzes the first three steps in de novo pyrimidine biosynthesis. The structural organization of the mammalian enzyme is very different fromE. coliATCase, a dodecameric, monofunctional molecule comprised of six copies of separate catalytic and regulatory chains. Nevertheless, sequence similarities and other properties suggested that the mammalian ATCase domain and theE. coliATCase catalytic chain have the same tertiary fold. A model of mammalian ATCase was built using the X‐ray coordinates of theE. colicatalytic chain as a tertiary template. Five small insertions and deletions could be readily accommodated in the model structure. Following energy minimization the RMS difference in the α carbon positions of the mammalian and bacterial proteins was 0.93 Å. A comparison of the hydrophobic energies, surface accessibility index, and the distribution of hydrophilic and hydrophobic residues of the CAD ATCase structure with correctly and incorrectly folded proteins and with several X‐ray structures supported the validity of the model. The mammalian ATCase domain associates to form a compact globular trimer, a prerequisite for catalysis since the active site is comprised of residues from adjacent subunits. Interactions between the clearly defined aspartate and carbamyl phosphate subdomains of the monomer were largely preserved while there was appreciable remodeling of the trimeric interfaces. Several clusters of basic residues are located on the upper surface of the domain which account in part for the elevated isoelectric point (pI= 9.4) and may represent contact regions with other more acidic domains within the chimeric polypeptide. A long interdomain linker connects the monomer at its upper surface to the remainder of the polypeptide. The configuration of active site residues is virtually identical in the mammalian and bacterial enzymes. While the CAD ATCase domain can undergo the local conformational changes that accompany catalysis in theE. colienzyme, the high activity, closed conformation is probably more stable in the mammalian e
ISSN:0887-3585
DOI:10.1002/prot.340090305
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1991
数据来源: WILEY
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5. |
Conformational perturbation of interleukin‐2: A strategy for the design of cytokine analogs |
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Proteins: Structure, Function, and Bioinformatics,
Volume 9,
Issue 3,
1991,
Page 207-216
Bryan E. Landgraf,
Diane P. Williams,
John R. Murphy,
Kendall A. Smith,
Thomas L. Ciardelli,
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摘要:
AbstractInterleukin‐2 (IL‐2) is a representative of a growing family of small proteins termed lymphokines which are responsible for mediating cell differentiation, growth and function in the immune system. Many of these proteins are being evaluated for their clinical potential. From the perspective of drug development, structure–function analysis of these molecules and their receptors require the use methodologies different than those traditionally employed for small peptides and other natural products. However, similar pharmacologic principles apply and an understanding of ligand‐receptor interactions and the asssociated responses is required in order to efficiently pursue agonist and antagonist design.Although IL‐2 is a protein of only 133 amino acid residues for which a low resolution X‐ray structure does exist, the complexity of its receptor system has provided an added challenge to structure–function studies. Consequently, little is known concerning the receptor contact residues for this protein. We have attempted to utilize established principles of protein and peptide structure to manipulate the conformation of IL‐2 in a manner which has provided analogs helpful for receptor interactions studies. These proteins have not only providing useful information on the nature of the IL‐2 receptor but have also revealed potential strategies for the design of IL‐2 agoni
ISSN:0887-3585
DOI:10.1002/prot.340090306
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1991
数据来源: WILEY
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6. |
Electron redistribution on binding of a substrate to an enzyme: Folate and dihydrofolate reductase |
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Proteins: Structure, Function, and Bioinformatics,
Volume 9,
Issue 3,
1991,
Page 217-224
Jürgen Bajorath,
David H. Kitson,
George Fitzgerald,
Jan Andzelm,
Joseph Kraut,
Arnold T. Hagler,
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摘要:
AbstractThe migration of electron density of a substrate (folate) on binding to an enzyme (dihydrofolate reductase) is studied by a quantum‐mechanical method originally developed in solid state physics. A significant polarization of the substrate is induced by the enzyme, toward the transition state of the enzymatic reaction, at the same time giving rise to “electronic strain energy” in the substrate and enhanced protein–ligand interactions. The spatial arrangement of protein charges that induces the polarization is identified and found to be structurally conserved for bacterial and vertebrate dihydrofolate red
ISSN:0887-3585
DOI:10.1002/prot.340090307
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1991
数据来源: WILEY
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7. |
Preliminary x‐ray analysis of crystals of plasminogen activator inhibitor‐1 |
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Proteins: Structure, Function, and Bioinformatics,
Volume 9,
Issue 3,
1991,
Page 225-227
Elizabeth J. Goldsmith,
Chen Sheng‐Cheng,
Dennis E. Danley,
Robert D. Gerard,
Kieran F. Geoghegan,
James Mottonen,
Arne Strand,
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摘要:
AbstractCrystals of bacterially expressed plasminogen activator inhibitor (PAI‐1) suitable for X‐ray diffraction analysis have been obtained from 8% (w/v) PEG 1500, pH 8.25. The space group isP1, and the lattice constants area= 82.17 Å,b= 47.82 Å,c= 62.89 Å, α = 90.00°, β = 106.90°, γ = 106.84°. The diffraction limit is 2.3 Å, and the unit cell contains two molecules of PAI‐1. The crystals contain latent PAI‐1 which can be partly reactivated by exposu
ISSN:0887-3585
DOI:10.1002/prot.340090308
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1991
数据来源: WILEY
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8. |
Masthead |
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Proteins: Structure, Function, and Bioinformatics,
Volume 9,
Issue 3,
1991,
Page -
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PDF (139KB)
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ISSN:0887-3585
DOI:10.1002/prot.340090301
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1991
数据来源: WILEY
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