Crystal structures of S-adenosylhomocysteine hydrolase from the thermophilic bacterium Thermotoga maritima

Zheng, Yingying; Chen, Chun‐Chi; Ko, Tzu‐Ping; Xiao, Xiansha; Yang, Yunyun; Huang, Chun‐Hsiang; Qian, Guojun; Shao, Weilan; Guo, Rey‐Ting

doi:10.1016/j.jsb.2015.03.002

Cited by 10 publications

(19 citation statements)

References 38 publications

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“…Moreover, a monovalent cation cannot be involved in the positioning of the lysine side chain. Indeed, the structure of archaeal-type SAHase from Thermotoga maritima crystallized in the presence of the SAH substrate does not contain any metal cation in the substrate binding region 12 .…”

Section: Resultsmentioning

confidence: 99%

Metal-cation regulation of enzyme dynamics is a key factor influencing the activity of S-adenosyl-l-homocysteine hydrolase from Pseudomonas aeruginosa

Czyrko

Sliwiak

Imiolczyk

et al. 2018

Sci Rep

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S-adenosyl-l-homocysteine hydrolase from Pseudomonas aeruginosa (PaSAHase) coordinates one K+ ion and one Zn2+ ion in the substrate binding area. The cations affect the enzymatic activity and substrate binding but the molecular mechanisms of their action are unknown. Enzymatic and isothermal titration calorimetry studies demonstrated that the K+ ions stimulate the highest activity and strongest ligand binding in comparison to other alkali cations, while the Zn2+ ions inhibit the enzyme activity. PaSAHase was crystallized in the presence of adenine nucleosides and K+ or Rb+ ions. The crystal structures show that the alkali ion is coordinated in close proximity of the purine ring and a 23Na NMR study showed that the monovalent cation coordination site is formed upon ligand binding. The cation, bound in the area of a molecular hinge, orders and accurately positions the amide group of Q65 residue to allow its interaction with the ligand. Moreover, binding of potassium is required to enable unique dynamic properties of the enzyme that ensure its maximum catalytic activity. The Zn2+ ion is bound in the area of a molecular gate that regulates access to the active site. Zn2+ coordination switches the gate to a shut state and arrests the enzyme in its closed, inactive conformation.

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Section: Resultsmentioning

confidence: 99%

Metal-cation regulation of enzyme dynamics is a key factor influencing the activity of S-adenosyl-l-homocysteine hydrolase from Pseudomonas aeruginosa

Czyrko

Sliwiak

Imiolczyk

et al. 2018

Sci Rep

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“…It is possible that the inter-domain cleft closes upon binding to ADO (or its analogues), although the crystal structure of the open form of MmSAHH has not yet been obtained. Recent crystal structures of SAHH from Thermotoga maritima (TmSAHH) 30 have shown that the binary complex (TmSAHH/NAD + ) adopts both open (space group C 2 crystal) and closed (space group P 3 1 21 crystal) conformations, despite the absence of bound nucleoside ligands. These observations indicate the flexible nature of the SAHH protomer and are consistent with the results from other crystal structure analyses of SAHHs from various species.…”

Section: Resultsmentioning

confidence: 99%

Structural insights into the reaction mechanism of S-adenosyl-L-homocysteine hydrolase

Kusakabe

Ishihara

Umeda

et al. 2015

Sci Rep

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S-adenosyl-L-homocysteine hydrolase (SAH hydrolase or SAHH) is a highly conserved enzyme that catalyses the reversible hydrolysis of SAH to L-homocysteine (HCY) and adenosine (ADO). High-resolution crystal structures have been reported for bacterial and plant SAHHs, but not mammalian SAHHs. Here, we report the first high-resolution crystal structure of mammalian SAHH (mouse SAHH) in complex with a reaction product (ADO) and with two reaction intermediate analogues—3’-keto-aristeromycin (3KA) and noraristeromycin (NRN)—at resolutions of 1.55, 1.55, and 1.65 Å. Each of the three structures constitutes a structural snapshot of one of the last three steps of the five-step process of SAH hydrolysis by SAHH. In the NRN complex, a water molecule, which is an essential substrate for ADO formation, is structurally identified for the first time as the candidate donor in a Michael addition by SAHH to the 3’-keto-4’,5’-didehydroadenosine reaction intermediate. The presence of the water molecule is consistent with the reaction mechanism proposed by Palmer & Abeles in 1979. These results provide insights into the reaction mechanism of the SAHH enzyme.

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“…SAHases are highly conserved proteins, therefore it is not surprising that their interactions with both ligands, as well as with the monovalent cation are very similar among SAHases of various origin. [3,4,[6][7][8][9]11,16] The Mode of Adenosine Binding The substrate-binding site of SAHases is formed by highly conserved amino acid residues. Therefore, the binding mode of Ado is similar to those observed in SAHases of various origin complexed with adenosine or its analogs.…”

Section: Enzyme-ligand Interactionsmentioning

confidence: 99%

“…SAHases usually function as 222-symmetric homotetramers, [4][5][6][7][8][9][10][11] or sometimes as homodimers. [3,12] Each subunit of the enzyme contains a tightly but noncovalently bound nicotinamide adenine dinucleotide cofactor in its oxidized form, NAD + .…”

Section: Introductionmentioning

confidence: 99%

Crystal Structure of S-adenosyl-L-homocysteine Hydrolase from Cytophaga hutchinsonii, a Case of Combination of Crystallographic and Non-crystallographic Symmetry

Czyrko¹,

Jaskólski²,

Brzeziński³

2018

Croat. Chem. Acta

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The majority of living organisms utilize S-adenosyl-L-homocysteine hydrolase (SAHase) as a key regulator of cellular methylation reactions. The unusual evolution history of SAHase genes is reflected in the phylogeny of these proteins, which are grouped into two major domains: mainly archaeal and eukaryotic/bacterial. Such a phylogeny is in contradiction to the three-domain topology of the tree of life, commonly based on 16S rRNA sequences. Within the latter domain, SAHases are classified as eukaryotic-only or bacterial-only clades depending on their origin and sequence peculiarities. A rare exception in this classification is SAHase from a cellulose-utilizing soil bacterium Cytophaga hutchinsonii (ChSAHase), as the phylogenetic analyses indicate that ChSAHase belongs to the animal clade. Here, the P21212 crystal structure of recombinant ChSAHase in ternary complex with the oxidized form of the NAD + cofactor and a reaction product/substrate (adenosine) is presented. Additionally, a sodium cation was identified in close proximity of the active site. The crystal contains two translational NCS-related intimate dimers of ChSAHase subunits in the asymmetric unit. Two complete tetrameric enzyme molecules are generated from these dimers within the crystal lattice through the operation of crystallographic twofold axes in the z direction.

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Crystal structures of S-adenosylhomocysteine hydrolase from the thermophilic bacterium Thermotoga maritima

Cited by 10 publications

References 38 publications

Metal-cation regulation of enzyme dynamics is a key factor influencing the activity of S-adenosyl-l-homocysteine hydrolase from Pseudomonas aeruginosa

Metal-cation regulation of enzyme dynamics is a key factor influencing the activity of S-adenosyl-l-homocysteine hydrolase from Pseudomonas aeruginosa

Structural insights into the reaction mechanism of S-adenosyl-L-homocysteine hydrolase

Crystal Structure of S-adenosyl-L-homocysteine Hydrolase from Cytophaga hutchinsonii, a Case of Combination of Crystallographic and Non-crystallographic Symmetry

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