Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the chemotaxis system of Escherichia coli, CheB promotes sensory adaptation by interacting with the chemotaxis receptor-transducer proteins to catalyze removal of their gamma-glutamyl methyl ester groups. CheB is comprised of two functional domains; the C-terminal domain contains the methylesterase active site, and the N-terminal domain regulates the activity of this active site. The chemotaxis system controls CheB methylesterase activity via a mechanism involving phosphorylation of the CheB regulatory domain by the chemotaxis protein kinase CheA. To further explore the communication between the regulatory and methylesterase domains of CheB, I generated mutations in the CheB regulatory domain that affect methylesterase activity in vitro. Three of these mutations (D11K, E58K, and E91K) caused increased methylesterase activity in the absence of phosphorylation, and several other mutations (R42H, R73H, and K107R) caused decreased methylesterase activity in the purified proteins. Several of these mutations (D10N, D11K, R42H, E58K, and K107R) also affected the phosphorylation biochemistry of CheB by reducing the rate of CheA-mediated phosphorylation of CheB and/or by decreasing the autodephosphorylation rate of CheB. In addition, all of these mutations diminished the ability of excess CheA to inhibit CheB methylesterase activity. The locations of these mutations in the deduced three-dimensional structure of the CheB N-terminal domain indicate that the region of the protein surrounding the putative phosphorylation site plays important roles in its interaction with the CheB C-terminal domain as well as in its interactions with CheA.
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PMID:Activating and inhibitory mutations in the regulatory domain of CheB, the methylesterase in bacterial chemotaxis. 842 Sep 65

Most motile bacteria are capable of directing their movement in response to chemical gradients, a behavior known as chemotaxis. The signal transduction system that mediates chemotaxis in enteric bacteria consists of a set of six cytoplasmic proteins that couple stimuli sensed by a family of transmembrane receptors to behavioral responses generated by the flagellar motors. Signal transduction occurs via a phosphotransfer pathway involving a histidine protein kinase, CheA, and a response regulator protein, CheY, that in its phosphorylated state, modulates the direction of flagellar rotation. Two auxiliary proteins, CheW and CheZ, and two receptor modification enzymes, methylesterase CheB and methyltransferase CheR, influence the flux of phosphoryl groups within this central pathway. This paper focuses on structural characteristics of the four signaling proteins (CheA, CheY, CheB, and CheR) for which NMR or x-ray crystal structures have been determined. The proteins are examined with respect to their signaling activities that involve reversible protein modifications and transient assembly of macromolecular complexes. A variety of data suggest conformational flexibility of these proteins, a feature consistent with their multiple roles in a dynamic signaling pathway.
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PMID:Structural analysis of bacterial chemotaxis proteins: components of a dynamic signaling system. 1004 6

Motile prokaryotes employ a chemoreceptor-kinase array to sense changes in the media and properly adjust their swimming behavior. This array is composed of a family of Type I membrane receptors, a histidine protein kinase (CheA), and an Src homology 3-like protein (CheW). Binding of an attractant to the chemoreceptors inhibits CheA, which results in decreased phosphorylation of the chemotaxis response regulator (CheY). Sensitivity of the system to stimuli is modulated by a protein methyltransferase (CheR) and a protein methylesterase (CheB) that catalyze the methylation and demethylation of specific glutamyl residues in the cytoplasmic domain of the receptors. One of the most fundamental unanswered questions concerning the bacterial chemotaxis mechanism is the quantitative relationship between ligand binding to receptors and CheA inhibition. We show that the receptor glutamyl modifications cause adaptation by changing the gain (magnitude amplification) between attractant binding and kinase inhibition without substantially affecting ligand binding affinity. The mechanism adjusts receptor sensitivity to background stimulus intensity over several orders of magnitude of attractant concentrations. The cooperative effects of ligand binding appear to be minimal with Hill coefficients for kinase inhibition less than 2, independent of the state of glutamyl modification.
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PMID:Receptor methylation controls the magnitude of stimulus-response coupling in bacterial chemotaxis. 1211 91

Bacterial chemotaxis is mediated by two reversible protein modification chemistries: phosphorylation and carboxyl methylation. Attractants bind to membrane chemoreceptors that control the activity of a protein kinase which acts in turn to control flagellar motor activity. Coordinate changes in receptor carboxyl methylation provide a negative feedback mechanism that serves a memory function. Protein carboxyl methylation might play an analogous role in the nervous system. Two protein carboxyl methyltransferases serve to regulate signal transduction pathways in eukaryotic cells. One is highly expressed in the Purkinje layer of the cerebellum where it methyl esterifies prenylated cysteine residues at the carboxyl-termini of Ras-related and heterotrimeric G-proteins. The other is abundant throughout the brain where it methylates the carboxyl-terminus of protein phosphatase 2A. The phosphatase methyltransferase and the protein methylesterase that reverses phosphatase methylation are structurally related to the corresponding bacterial chemotaxis methylating and demethylating enzymes. Recent results indicate that deficiencies in phosphatase methylation play an important role in the etiology of Alzheimer's disease.
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PMID:Protein carboxyl methylation and the biochemistry of memory. 1974 79