Structure of Acetylglutamate Kinase, a Key Enzyme for Arginine Biosynthesis and a Prototype for the Amino Acid Kinase Enzyme Family, during Catalysis

Ramón‐Maiques, Santiago; Marina, Alberto; Gil-Ortiz, F.; Fita, Ignacio; Rubio, Vicente

doi:10.1016/s0969-2126(02)00721-9

Cited by 125 publications

(219 citation statements)

References 52 publications

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“…S1). Other protein structures with a similar fold include NAGK (11,12), carbamate kinase (36), carbamate kinase-like CPS (37), UMP kinase (38, 39), aspartokinase (40), and 5-glutamate kinase (41). Superimposition of this domain with the closely related Thermotoga maritima and Pseudomonas aeruginosa NAGK structures yields a root mean square deviation of 1.7 and 1.6 Å for the 238 and 234 equivalent C␣ atoms, respectively.…”

Section: Resultsmentioning

confidence: 99%

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The Crystal Structure of N-Acetyl-L-glutamate Synthase from Neisseria gonorrhoeae Provides Insights into Mechanisms of Catalysis and Regulation

Shi

Sagar

Jin

et al. 2008

Journal of Biological Chemistry

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Section: Resultsmentioning

confidence: 99%

“…Several NAGK-related and many NAT-related structures have been determined (11)(12)(13)(14). However, no NAGS structure from any organism has been previously reported, probably because most NAGS proteins are unstable and not amendable to crystallization (15).…”

mentioning

confidence: 99%

The Crystal Structure of N-Acetyl-L-glutamate Synthase from Neisseria gonorrhoeae Provides Insights into Mechanisms of Catalysis and Regulation

Shi

Sagar

Jin

et al. 2008

Journal of Biological Chemistry

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“…Apart from the two additional helices a2 and a3, the AK1 N-terminal domain shows strong structural similarity to the catalytic domain of three members of this family: acetylglutamate kinase (NAGK; PDB code 1gs5; 163/259 Ca atoms matched, RMS distance 1.8 Å ) (Ramon-Maiques et al, 2002), urydilate kinase (UMPK; PDB code 2bmu; 150/225 Ca atoms matched, RMS distance 1.7 Å ), and carbamate kinase-like carbamoyl phosphate synthetase (CBMK; PDB code 1e19; 128/313 Ca atoms matched, RMS distance 1.7 Å ) (RamonMaiques et al, 2000) structures.…”

Section: Domain Organizationmentioning

confidence: 99%

A Novel Organization of ACT Domains in Allosteric Enzymes Revealed by the Crystal Structure of Arabidopsis Aspartate Kinase

et al. 2006

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Asp kinase catalyzes the first step of the Asp-derived essential amino acid pathway in plants and microorganisms. Depending on the source organism, this enzyme contains up to four regulatory ACT domains and exhibits several isoforms under the control of a great variety of allosteric effectors. We report here the dimeric structure of a Lys and S-adenosylmethionine-sensitive Asp kinase isoform from Arabidopsis thaliana in complex with its two inhibitors. This work reveals the structure of an Asp kinase and an enzyme containing two ACT domains cocrystallized with its effectors. Only one ACT domain (ACT1) is implicated in effector binding. A loop involved in the binding of Lys and S-adenosylmethionine provides an explanation for the synergistic inhibition by these effectors. The presence of S-adenosylmethionine in the regulatory domain indicates that ACT domains are also able to bind nucleotides. The organization of ACT domains in the present structure is different from that observed in Thr deaminase and in the regulatory subunit of acetohydroxyacid synthase III.

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“…We previously determined the structures of arginineinsensitive (16) and arginine-sensitive NAGKs (17). The latter are hexameric ring-like trimers of dimers with a central hole of 25-30 Å, in which the dimers resemble the homodimeric arginine-insensitive enzyme (16). The NAGK subunit is an open ␣ 3 ␤ 8 ␣ 4 sandwich that can be divided into a N-domain and a C-domain.…”

mentioning

confidence: 99%

The crystal structure of the complex of P _II and acetylglutamate kinase reveals how P _II controls the storage of nitrogen as arginine

Llácer

Contreras

Forchhammer

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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105

165

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Photosynthetic organisms can store nitrogen by synthesizing arginine, and, therefore, feedback inhibition of arginine synthesis must be relieved in these organisms when nitrogen is abundant. This relief is accomplished by the binding of the P II signal transduction protein to acetylglutamate kinase (NAGK), the controlling enzyme of arginine synthesis. Here, we describe the crystal structure of the complex between NAGK and P II of Synechococcus elongatus, at 2.75-Å resolution. We prove the physiological relevance of the observed interactions by site-directed mutagenesis and functional studies. The complex consists of two polar P II trimers sandwiching one ring-like hexameric NAGK (a trimer of dimers) with the threefold axes of these molecules aligned. The binding of P II favors a narrow ring conformation of the NAGK hexamer that is associated with arginine sites having low affinity for this inhibitor. Each PII subunit contacts one NAGK subunit only. The contacts map in the inner circumference of the NAGK ring and involve two surfaces of the P II subunit. One surface is on the PII body and interacts with the C-domain of the NAGK subunit, helping widen the arginine site found on the other side of this domain. The other surface is at the distal region of a protruding large loop (T-loop) that presents a novel compact shape. This loop is inserted in the interdomain crevice of the NAGK subunit, contacting mainly the N-domain, and playing key roles in anchoring P II on NAGK, in activating NAGK, and in complex formation regulation by MgATP, ADP, 2-oxoglutarate, and by phosphorylation of serine-49.arginine synthesis ͉ regulation ͉ x-ray structure ͉ signaling ͉ cyanobacteria I n photosynthetic organisms nitrogen can be stored by synthesizing arginine (1, 2) and, therefore, feedback inhibition of arginine synthesis must be relieved when nitrogen is abundant. The enzyme of arginine biosynthesis that is the target of arginine inhibition, N-acetyl-L-glutamate (NAG) kinase (NAGK) (1, 3-5), was found in cyanobacteria and plants (2, 4-8) to be a target of the carbon/ nitrogen P II signaling protein (9, 10), forming with it a complex in which arginine inhibition is alleviated (6, 7). P II signaling proteins are homotrimers of a 12-to 13-kDa subunit that interact with enzymes, transcription factors, and ammonia channels, regulating their activity (9, 10) and carbon/ nitrogen homeostasis. Numerous structures of P II proteins, including those for cyanobacteria and plants (9-12), are known, but it was unclear how P II proteins carry out their functions. The body of the P II trimer is roughly hemispheric. Its subunits have ␤␣␤␤␣␤ topology, with ␣ helices looking outward and the ␤ sheet inward and providing the intersubunit interactions. Each subunit has three loops: the B-and C-loops and the larger flexible T-loop. The T-loop residues Y51 and S49 are, respectively, the sites of the regulatory uridylylation and phosphorylation in enterobacterial and cyanobacterial P II proteins (9, 10), with S49 phosphorylation abolishing interaction wi...

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Structure of Acetylglutamate Kinase, a Key Enzyme for Arginine Biosynthesis and a Prototype for the Amino Acid Kinase Enzyme Family, during Catalysis

Cited by 125 publications

References 52 publications

The Crystal Structure of N-Acetyl-L-glutamate Synthase from Neisseria gonorrhoeae Provides Insights into Mechanisms of Catalysis and Regulation

The Crystal Structure of N-Acetyl-L-glutamate Synthase from Neisseria gonorrhoeae Provides Insights into Mechanisms of Catalysis and Regulation

A Novel Organization of ACT Domains in Allosteric Enzymes Revealed by the Crystal Structure of Arabidopsis Aspartate Kinase

The crystal structure of the complex of P _II and acetylglutamate kinase reveals how P _II controls the storage of nitrogen as arginine

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Structure of Acetylglutamate Kinase, a Key Enzyme for Arginine Biosynthesis and a Prototype for the Amino Acid Kinase Enzyme Family, during Catalysis

Cited by 125 publications

References 52 publications

The Crystal Structure of N-Acetyl-L-glutamate Synthase from Neisseria gonorrhoeae Provides Insights into Mechanisms of Catalysis and Regulation

The Crystal Structure of N-Acetyl-L-glutamate Synthase from Neisseria gonorrhoeae Provides Insights into Mechanisms of Catalysis and Regulation

A Novel Organization of ACT Domains in Allosteric Enzymes Revealed by the Crystal Structure of Arabidopsis Aspartate Kinase

The crystal structure of the complex of P II and acetylglutamate kinase reveals how P II controls the storage of nitrogen as arginine

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Product

Resources

About

The crystal structure of the complex of P _II and acetylglutamate kinase reveals how P _II controls the storage of nitrogen as arginine