Structural Studies of Intermediates along the Cyclization Pathway of Aplysia ADP-Ribosyl Cyclase

Kotaka, Masayo; Graeff, Richard; Chen, Zhe; Zhang, Li He; Lee, Hon Cheung; Hao, Quan

doi:10.1016/j.jmb.2011.11.022

Cited by 12 publications

(34 citation statements)

References 32 publications

(51 reference statements)

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“…The polypeptide backbones of all of these molecules superimpose well, but each has the covalent intermediate in a different conformation (80). Similar results were obtained with the cyclase, and eight molecules are seen in each unit (79). All of the conformations of the intermediate can be mapped to each other by single-bond rotation (71, 79, 80), indicating they are substates of the cyclization process.…”

Section: Catalytic Mechanisms Of Cd38 and The Cyclasesupporting

confidence: 65%

“…The most novel of these catalytic reactions, the cyclization of NAD, has recently been visualized (79,80). When a close analog of NAD, 2Ј-deoxy-2Ј-fluoroarabinoside NAD, is used as substrate, it is hydrolyzed like NAD to release the nicotinamide group, but its anomeric carbon of the terminal ribose then forms a covalent linkage with the catalytic residue Glu-226 (80).…”

Section: Catalytic Mechanisms Of Cd38 and The Cyclasementioning

confidence: 99%

“…A movie of the process can be made by ordering these substates (see supplemental data in Ref. 79), revealing that the folding of the linear substrate involves a major rotation of the adenine ring around its ribosyl bond, such that its N1 position is oriented toward the cyclization site, the C1 of the terminal ribose (Fig. 3).…”

Section: Catalytic Mechanisms Of Cd38 and The Cyclasementioning

confidence: 99%

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Cyclic ADP-ribose and Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) as Messengers for Calcium Mobilization

Lee

2012

Journal of Biological Chemistry

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Cyclic ADP-ribose and nicotinic acid adenine dinucleotide phosphate were discovered >2 decades ago. That they are second messengers for mobilizing Ca 2؉ stores has since been firmly established. Separate stores and distinct Ca 2؉ channels are targeted, with cyclic ADP-ribose acting on the ryanodine receptors in the endoplasmic reticulum, whereas nicotinic acid adenine dinucleotide phosphate mobilizes the endolysosomes via the two-pore channels. Despite the structural and functional differences, both messengers are synthesized by a ubiquitous enzyme, CD38, whose crystal structure and catalytic mechanism have now been well elucidated. How this novel signaling enzyme is regulated remains largely unknown and is the focus of this minireview.

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Section: Catalytic Mechanisms Of Cd38 and The Cyclasesupporting

confidence: 65%

Section: Catalytic Mechanisms Of Cd38 and The Cyclasementioning

confidence: 99%

Section: Catalytic Mechanisms Of Cd38 and The Cyclasementioning

confidence: 99%

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Cyclic ADP-ribose and Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) as Messengers for Calcium Mobilization

Lee

2012

Journal of Biological Chemistry

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176

178

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“…It can also hydrolyze both NAADP and NADP to ADPRP. by capturing the multiple conformation states of reaction intermediates in a single crystal (Kotaka et al, 2012;Zhang et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Crystal Structures of Human CD38 in Complex with NAADP and ADPRP

Zhang¹,

Graeff²,

Lee³

et al. 2013

messenger

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Mobilization of intracellular Ca 2+ stores is a critical process for many cell activities. Nicotinic acid adenine dinucleotide phosphate (NAADP) is a novel second messenger that can mobilize acidic calcium stores, such as the endo-lysosomes. It is thus functionally distinct from the two other Ca 2+ signaling messengers, cyclic ADP-ribose and inositol trisphosphate, which target the Ca 2+ stores in the endoplasmic reticulum. Human CD38, a multifunctional protein having both receptor and enzymatic roles in almost all cell types, has been shown to catalyze both the synthesis and degradation of NAADP. Here, we present the first image of this novel messenger in complex with human CD38 as captured by X-ray crystallography. The results provide insight into the degradation mechanism of NAADP by human CD38.

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“…Crystals with six molecules in an asymmetric unit were obtained, and all of them had structures of ara-F-ADPR covalently bound to residue Glu226 in different conformations: half of them were in the cyclizing (N1) conformation, and the other half were in the non-cyclizing conformation (N7). In contrast to formation of a covalent intermediate, the enzymatic cleavage of the nicotinamide-glycosidic bond of NAD + was also proposed to occur through an oxocarbenium ion-like transition state (Oppenheimer, 1994;MullerSteffner et al, 1996;Liu et al, 2006;Liu et al, 2008;Kotaka et al, 2012). Lee and colleagues gave a systematic exposition on the solution of a series of CD38-substrate complex crystal structures.…”

Section: Catalytic Mechanism Of Cd38mentioning

confidence: 99%

Studies on CD38 Inhibitors and Their Application to cADPR-Mediated Ca<SUP>2</SUP><SUP>+</SUP> Signaling

Liu¹,

Graeff²,

Jin³

et al. 2013

messenger

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CD38 is a multifunctional protein involved in many cellular functions and has both antigenic and enzymatic properties. It catalyzes the synthesis of the calcium mobilizing messenger molecules cyclic adenosine 5'-diphosphoribose (cADPR), adenosine 5'-diphosphoribose (ADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP), which stimulate ryanodine, TRPM2, and two-pore channels, respectively. Gene knock-out experiments have shown that CD38 is closely linked to specific physiological responses that result from cADPR-dependent changes in intracellular calcium concentration. Because CD38 plays important roles in signaling pathways that may contribute to human pathologies, it is a potential target for drug development. In the past decade, considerable progress has been made toward the discovery and development of CD38 inhibitors. This review is aimed at giving a brief insight into the progress made to date about CD38 inhibitors, primarily regarding their specificity of inhibitory activity and their importance to cADPR-mediated Ca 2+ signaling.

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Structural Studies of Intermediates along the Cyclization Pathway of Aplysia ADP-Ribosyl Cyclase

Cited by 12 publications

References 32 publications

Cyclic ADP-ribose and Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) as Messengers for Calcium Mobilization

Cyclic ADP-ribose and Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) as Messengers for Calcium Mobilization

Crystal Structures of Human CD38 in Complex with NAADP and ADPRP

Studies on CD38 Inhibitors and Their Application to cADPR-Mediated Ca<SUP>2</SUP><SUP>+</SUP> Signaling

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