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Protein Structures Determined in the Stock Laboratory


CheY-Mg2+ | CheBc | CheB | CheR | CheR-peptide | OmpRc | DrrD | Der | NPC2 | DrrB


 



CheY-Mg2+

Salmonella typhimurium CheY with Mg2+ bound at the active site (1.8 A). CheY is a response regulator protein that controls the direction of rotation of bacterial flagellar filaments during chemotaxis. The structure of CheY with Mg2+ bound at the active site suggests a mechanism for phosphoryl transfer involving a pentavalent phosphorus intermediate. This mechanism is postulated to be applicable to other members of the large response regulator family.
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Download coordinates (2CHE)


Stock, A.M., Martinez-Hackert, E., Rasmussen, B.F., West, A., Stock, J.B., Ringe, D. and Petsko, G.A. (1993) Structure of the Mg
2+-bound form of CheY and mechanism of phosphoryl transfer in bacterial chemotaxis. Biochemistry 32(49):13375-13380.
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CheBc

Salmonella typhimurium methylesterase CheB catalytic domain (1.75 ?). Methylesterase CheB catalyzes the demethylation of methylglutatmate residues in bacterial chemoreceptors. CheB, together with methyltransferase CheR are important for adaption during chemotaxis. The structure of the catalytic domain of CheB defined the active site, a catalytic triad involving Ser164, His190, and Asp286, similar to the active sites of other serine hydrolase enzymes.
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Download coordinates (1CHD)


West, A.H., Martinez-Hackert, E. and Stock, A.M. (1995) Crystal structure of the catalytic domain of the chemotaxis receptor methylesterase, CheB. J. Mol. Biol. 250(2):276-290.
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CheB

Salmonella typhimurium methylesterase CheB (2.4 A). Methylesterase CheB is one of two enzymes that catalyze the reversible modification of chemotaxis transmembrane receptors, a process that contributes to adaptation. CheB is a respone regulator protein whose activity is regulated by phosphorylation. The structure of intact CheB suggests a mechanism for inhibition of the activity of the C- terminal catalytic domain by the unphosphorylated N-terminal regulatory domain which packs against the active site, sterically blocking access of substrate.
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Download coordinates (1A2O)


Djordjevic, S., Goudreau, P.N., Xu, Q., Stock, A.M. and West, A.H. (1998) Structural basis for methylesterase CheB regulation by a phosphorylation- activated domain. Proc. Natl. Acad. Sci. USA 95(4):1381-1386.
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CheR

Salmonella typhimurium methyltransferase CheR (2.0 A). Methyltransferase CheR catalyzes the reversible methylation of glutamate residues in the cytoplasmic domains of bacterial chemoreceptors. The structure of cheR provided the first structural information for a protein methyltransferase. Despite a lack of sequence similarity with other DNA, RNA, and small molecule methyltransferases, the fold of the co-factor binding domain and the conformation of the S-adenosyl methionine binding site are conserved.
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Download coordinates (1AF7)


Djordjevic, S. and Stock, A.M. (1997) Crystal structure of the chemotaxis receptor methyltransferase CheR suggests a conserved structural motif for binding S-adenosylmethionine. Structure 5(4):545-558.
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CheR-peptide

Salmonella typhimurium methyltransferase CheR bound to a pentapeptide of the aspartate chemoreceptor Tar (2.20 A). Methyltransferase CheR is a chemotaxis receptor modification enzyme. CheR binds to a pentapeptide located at the C- termini of some chemoreceptors. From this tethered position, CheR methylates specific glutamate residues located distally within the chemoreceptor cytoplasmic domains. The co-factor binding domain of all receptor methyltransferases contains a novel small beta sheet subdomain that is the binding site for the receptor pentapeptide.
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Download coordinates (1BC5)


Djordjevic, S. and Stock, A.M. (1998) Chemotaxis receptor recognition by protein methyltransferase CheR. Nature Struct. Biol. 5(6):446- 450.
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OmpRc

Escherichia coli OmpR DNA- binding domain (1.95 A). OmpR is a transcription factor that differentially regulates expression of genes encoding the outer membrane porin proteins OmpF and OmpC in response to osmotic strength. OmpR is a representative member of a subfamily of response regualtor proteins characterized by conserved DNA-binding domains. The structure of OmpRc established the fold of this DNA-binding domain, a modified winged-helix fold.
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Download coordinates (1OPC)


Martinez-Hackert, E. and Stock, A.M. (1997) The DNA-binding domain of OmpR: crystal structure of a winged helix transcription factor. Structure 5(1):109-124.
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DrrD

Thermotoga maritima transcription factor DrrD (1.50 A). DrrD is a response regulator that belongs to the OmpR/PhoB subfamily, a group that accounts for approximately half of all response regulator transcription factors. The genes regulated by DrrD are unknown. DrrD provides the first structural information for an intact response regulator of the OmpR/PhoB family. The small domain interface distinguishes DrrD from all other multidomain response regulators for which structures have been solved, and suggests that the OmpR/PhoB subfamily may employ a different mechanism of regulation.
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Download coordinates (1KGS)


Buckler, D.R., Zhou, Y. and Stock, A.M. (2002) Evidence of intradomain and interdomain flexibility in an OmpR/PhoB homolog from Thermotoga maritima. Structure 10: 153-164.
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Der

Thermotoga maritima GTPase Der (1.9 A). Der is a member of the EngA subfamily of essential bacterial GTPases. Der has a unique domain structure consisting of two adjacent GTPAse domains and a C-terminal KH domain that lacks the distinctive RNA recognition elements. The structure of Der provides the first structural information for a member of the EngA subfamily and establishes a novel domain achitecture in which the GTPAse domains pack at either side of the C-terminal domain. The interdomain contacts observed in the structure provide a foundation for investigating mechanisms of intramolecular regulation within this bacterial switch protein.
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Download coordinates (1MKY)


Robinson, V.L., Hwang, J., Fox, E., Inouye, M. and Stock, A.M. (2002) Domain arrangement of Der, a switch protein containing two GTPase domains. Structure 10: 1649-1658.
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NPC2

Bovine NPC2 Cholesterol-Binding Protein (1.7 A). Niemann-Pick disease type C2 (NP-C2) is a fatal hereditary disease characterized by accumulation of low density lipoprotein (LDL) -derived cholesterol in lysosomes. NP-C2 disease is caused by a deficiency in NPC2 protein, a soluble lysosomal cholesterol-binding protein. NPC2 has an immunoglobulin-like fold stabilized by three disulfide bonds. The structure of the bovine protein reveals a loosely packed region penetrating from the surface into the hydrophobic core that forms adjacent small cavities with a total volume of ~160 A3. We propose that this represents the incipient cholesterol-binding site that dilates to accommodate an ~740 A3 cholesterol molecule.
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Download coordinates (1NEP)


Friedland, N., Liou, H.-L., Lobel, P. and Stock, A.M. (2003) Structure of a cholesterol-binding protein deficient in Niemann-Pick type C2 disease. Proc. Natl. Acad. Sci. U.S.A. 100: 2512-2517.
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DrrB

Thermotoga maritima transcription factor DrrB (1.80 A). DrrB is one of four response regulators of the OmpR/PhoB subfamily encoded in the genome of Thermotoga maritima. Although little is known of the function of the Drr proteins, they have served as good models for structural analysis of OmpR/PhoB subfamily members. DrrB and DrrD provide the only structural information available for this large family of proteins. Unlike DrrD, the DrrB protein contains a large domain interface that is presumably altered by phosphorylation. The extremely different domain arrangements in DrrB and DrrD suggest fundamentally different intra- and inter-molecular mechanisms of regulation in these two family members.
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Download coordinates (1P2F)


Robinson, V.L., Wu, T. and Stock, A.M. (2003) Structural analysis of the domain interface in DrrB, a response regulator of the OmpR/PhoB subfamily. J. Bacteriol. 185: 4186-4194.
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