Identification of the Active Site Catalytic Residue in Human Isovaleryl-CoA Dehydrogenase

Biochemistry ◽  
1995 ◽  
Vol 34 (32) ◽  
pp. 10146-10152 ◽  
Author(s):  
Al-Walid A. Mohsen ◽  
Jerry Vockley
Keyword(s):  
Active Site ◽  
Catalytic Residue

scholarly journals Snake venom NAD glycohydrolases: primary structures, genomic location, and gene structure

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6154 ◽  
Author(s):  
Ivan Koludarov ◽  
Steven D. Aird
Keyword(s):  
Snake Venom ◽  
Active Site ◽  
Disulfide Bonds ◽  
Venom Gland ◽  
Catalytic Residue ◽  
Nad Glycohydrolase ◽  
Adp Ribosyl Cyclase ◽  
Genomic Location ◽  
Cyclic Adp Ribose ◽  
Very High

NAD glycohydrolase (EC 3.2.2.5) (NADase) sequences have been identified in 10 elapid and crotalid venom gland transcriptomes, eight of which are complete. These sequences show very high homology, but elapid and crotalid sequences also display consistent differences. As in Aplysia kurodai ADP-ribosyl cyclase and vertebrate CD38 genes, snake venom NADase genes comprise eight exons; however, in the Protobothrops mucrosquamatus genome, the sixth exon is sometimes not transcribed, yielding a shortened NADase mRNA that encodes all six disulfide bonds, but an active site that lacks the catalytic glutamate residue. The function of this shortened protein, if expressed, is unknown. While many vertebrate CD38s are multifunctional, liberating both ADP-ribose and small quantities of cyclic ADP-ribose (cADPR), snake venom CD38 homologs are dedicated NADases. They possess the invariant TLEDTL sequence (residues 144–149) that bounds the active site and the catalytic residue, Glu228. In addition, they possess a disulfide bond (Cys121–Cys202) that specifically prevents ADP-ribosyl cyclase activity in combination with Ile224, in lieu of phenylalanine, which is requisite for ADPR cyclases. In concert with venom phosphodiesterase and 5′-nucleotidase and their ecto-enzyme homologs in prey tissues, snake venom NADases comprise part of an envenomation strategy to liberate purine nucleosides, and particularly adenosine, in the prey, promoting prey immobilization via hypotension and paralysis.

scholarly journals Tyrosine 121 moves revealing a druggable pocket that couples catalysis to ATP-binding in serine racemase

2021 ◽  
Author(s):  
Chloe R. Koulouris ◽  
Sian E. Gardiner ◽  
Tessa K. Harris ◽  
Karen T. Elvers ◽  
S. Mark Roe ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Active Site ◽  
Serine Racemase ◽  
Hydroxyl Group ◽  
Catalytic Residue ◽  
Dimer Interface ◽  
X Ray ◽  
The Core ◽  
Small Domain ◽  
Allosteric Activator

ABSTRACTHuman serine racemase (hSR) catalyses racemisation of L-serine to D-serine, the latter of which is a co-agonist of the NMDA subtype of glutamate receptors that are important in synaptic plasticity, learning and memory. In a ‘closed’ hSR structure containing the allosteric activator ATP, the inhibitor malonate is enclosed between the large and small domains while ATP is distal to the active site, residing at the dimer interface with the Tyr121 hydroxyl group contacting the ATP a-phosphate. In contrast, in ‘open’ hSR structures, Tyr121 sits in the core of the small domain with its hydroxyl contacting the key catalytic residue Ser84. The ability to regulate SR activity by flipping Tyr121 from the core of the small domain to the dimer interface appears to have evolved in animals with a CNS. Multiple X-ray crystallographic enzymefragment structures show that Tyr121 is flipped out of its pocket, suggesting that this pocket is druggable.

Locating Al in the DABCO catalyst before and after Al extraction

1990 ◽  
Vol 48 (4) ◽  
pp. 265-267
Author(s):  
Kathleen B. Reuter
Keyword(s):  
Active Site ◽  
Inverse Relationship ◽  
Transverse Direction ◽  
Reaction Rate ◽  
Acid Phosphate ◽  
Fracture Surfaces ◽  
Al Content ◽  
Before And After ◽  
Relationship Of

The reaction rate and efficiency of piperazine to 1,4-diazabicyclo-octane (DABCO) depends on the Si/Al ratio of the MFI topology catalysts. The Al was shown to be the active site, however, in the Si/Al range of 30-200 the reaction rate increases as the Si/Al ratio increases. The objective of this work was to determine the location and concentration of Al to explain this inverse relationship of Al content with reaction rate.Two silicalite catalysts in the form of 1/16 inch SiO2/Al2O3 bonded extrudates were examined: catalyst A with a Si/Al of 83; and catalyst B, the acid/phosphate Al extracted form of catalyst A, with a Si/Al of 175. Five extrudates from each catalyst were fractured in the transverse direction and particles were obtained from the fracture surfaces near the center of the extrudate diameter. Particles were also obtained from the outside surfaces of five extrudates.

Structures of c-di-GMP/cGAMP degrading phosphodiesterase VcEAL: identification of a novel conformational switch and its implication

2019 ◽  
Vol 476 (21) ◽  
pp. 3333-3353 ◽  
Author(s):  
Malti Yadav ◽  
Kamalendu Pal ◽  
Udayaditya Sen
Keyword(s):  
Active Site ◽  
Metal Binding ◽  
Metal Ion ◽  
Triosephosphate Isomerase ◽  
Catalytic Mechanism ◽  
Degradation Mechanism ◽  
Structural Basis ◽  
Conserved Residues ◽  
Phosphodiester Bond ◽  
Cyclic Dinucleotides

Cyclic dinucleotides (CDNs) have emerged as the central molecules that aid bacteria to adapt and thrive in changing environmental conditions. Therefore, tight regulation of intracellular CDN concentration by counteracting the action of dinucleotide cyclases and phosphodiesterases (PDEs) is critical. Here, we demonstrate that a putative stand-alone EAL domain PDE from Vibrio cholerae (VcEAL) is capable to degrade both the second messenger c-di-GMP and hybrid 3′3′-cyclic GMP–AMP (cGAMP). To unveil their degradation mechanism, we have determined high-resolution crystal structures of VcEAL with Ca2+, c-di-GMP-Ca2+, 5′-pGpG-Ca2+ and cGAMP-Ca2+, the latter provides the first structural basis of cGAMP hydrolysis. Structural studies reveal a typical triosephosphate isomerase barrel-fold with substrate c-di-GMP/cGAMP bound in an extended conformation. Highly conserved residues specifically bind the guanine base of c-di-GMP/cGAMP in the G2 site while the semi-conserved nature of residues at the G1 site could act as a specificity determinant. Two metal ions, co-ordinated with six stubbornly conserved residues and two non-bridging scissile phosphate oxygens of c-di-GMP/cGAMP, activate a water molecule for an in-line attack on the phosphodiester bond, supporting two-metal ion-based catalytic mechanism. PDE activity and biofilm assays of several prudently designed mutants collectively demonstrate that VcEAL active site is charge and size optimized. Intriguingly, in VcEAL-5′-pGpG-Ca2+ structure, β5–α5 loop adopts a novel conformation that along with conserved E131 creates a new metal-binding site. This novel conformation along with several subtle changes in the active site designate VcEAL-5′-pGpG-Ca2+ structure quite different from other 5′-pGpG bound structures reported earlier.

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