Crystal Structure of Human Guanosine Monophosphate Reductase 2 (GMPR2) in Complex with GMP

Li, Jixi; Wei, Zhiyi; Zheng, Mou‐Xiong; Gu, Xing; Deng, Yingfeng; Qiu, Rui; Chen, Fei; Ji, Chaoneng; Gong, Weimin; Xie, Yi; Mao, Yumin

doi:10.1016/j.jmb.2005.11.047

Cited by 28 publications

(58 citation statements)

References 33 publications

(64 reference statements)

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“…The residues Phe280, Ile294, Tyr297, Arg310, Gly312, and Val329 appeared in non-bonded contacts at the dimeric interface. To achieve catalytic activity and maintain thermostability, dimerization of two monomers is essential in HSL family enzymes192021. In addition, we mutated 11 amino acid residues that are involved in the dimeric surface (E285A, R298A, K308A, C309A, Q311A, M313A, D328A, R331A, D332A, and S336A) (Fig.…”

Section: Resultsmentioning

confidence: 99%

Structural insights of a hormone sensitive lipase homologue Est22

Huang

Huo

et al. 2016

Sci Rep

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Hormone sensitive lipase (HSL) catalyzes the hydrolysis of triacylglycerols into fatty acids and glycerol, thus playing key roles in energy homeostasis. However, the application of HSL serving as a pharmaceutical target and an industrial biocatalyst is largely hampered due to the lack of high-resolution structural information. Here we report biochemical properties and crystal structures of a novel HSL homologue esterase Est22 from a deep-sea metagenomic library. Est22 prefers short acyl chain esters and has a very high activity with substrate p-nitrophenyl butyrate. The crystal structures of wild type and mutated Est22 with its product p-nitrophenol are solved with resolutions ranging from 1.4 Å to 2.43 Å. The Est22 exhibits a α/β-hydrolase fold consisting with a catalytic domain and a substrate-recognizing cap domain. Residues Ser188, Asp287, and His317 comprise the catalytic triad in the catalytic domain. The p-nitrophenol molecule occupies the substrate binding pocket and forms hydrogen bonds with adjacent residues Gly108, Gly109, and Gly189. Est22 exhibits a dimeric form in solution, whereas mutants D287A and H317A change to polymeric form, which totally abolished its enzymatic activities. Our study provides insights into the catalytic mechanism of HSL family esterase and facilitates the understanding for further industrial and biotechnological applications of esterases.

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Section: Resultsmentioning

confidence: 99%

Structural insights of a hormone sensitive lipase homologue Est22

Huang

Huo

et al. 2016

Sci Rep

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“…IMPDH catalyzes the formation of XMP from IMP, a rate-limiting reaction of de novo GTP biosynthesis, and is associated with cell proliferation and neoplastic cell transformation (Markham et al 1999), which makes it a target for anticancer, antiviral, antimicrobial, antiprotozoan therapies (Franchetti & Grifantini 1999, Hedstrom 1999, Sullivan et al 2005. GMPR catalyzes the reductive deamination of GMP to IMP, and plays an important role in maintaining the intracellular balance of A and G nucleotides (Li et al 2006). The clones encoding protein kinase domaincontaining protein were the fourth most abundant clones (21 clones).…”

Section: Resultsmentioning

confidence: 99%

Identification of differentially expressed genes in parasitic phase Miamiensis avidus (Ciliophora: Scuticociliatia) using suppression subtractive hybridization

Lee¹,

Kim²

2011

Dis. Aquat. Org.

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Miamiensis avidus, a causative agent of scuticociliatosis in cultured marine fish, can live not only in seawater as a free-living organism but also in fish as a parasite. In this study, a cDNA library of representative mRNAs more specific to parasitic phase M. avidus was generated using suppression subtractive hybridization (SSH), and 520 clones selected from the SSH library were singlerun sequenced. The differential gene expression patterns were confirmed by semi-quantitative reverse-transcription PCR. Of the 510 SSH clones, 21 clones of 6 putative genes did not match sequences in the public database. The expectation values (E-values) of 117 clones encoding 9 putative genes were greater than 1 × 10 -5. The other 372 clones that met the criterion of E value <1 × 10 -5 were matched to 26 known sequences in the database. Genes associated with signal transduction, cell proliferation, membrane transportation, protein translocation, and transcription regulation were preferentially expressed in parasitic phase M. avidus. The differential gene expression may be needed for the ciliates to survive in the host fish, and the corresponding proteins might be used as antigen candidates for development of scuticociliatosis vaccines.

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“…The enzyme has been purified from a handful of sources: Aerobacter aerogenes (Mager and Magasanik, 1960, Brox and Hampton, 1968), human erythrocytes (Mackenzie and Sorensen, 1973, Spector, 1979 #838), calf thymus (Stephens and Whittaker, 1973), Leishmania donvani (Spector and Jones, 1982, Spector et al, 1984), Artemia salina (Renart et al, 1976a, Renart et al, 1976b), though its presence has been inferred in several other cases by the conversion of labeled guanine into adenine nucleotides. Only the human and Escherichia coli genes have been cloned and expressed to verify activity (Andrews and Guest, 1988, Moffat and Mackinnon, 1985, Martinelli et al, 2011, Patton et al, 2011, Li et al, 2006, Zhang et al, 2003, Deng et al, 2002). X-ray crystal structures are available for human GMPR1 and GMPR2 in several complexes: E•GMP (2ble, 2bwg, 2a7r, (Li et al, 2006)), E•IMP (2bzn, (Patton et al, 2011)) and E•IMP•NADH (2c6q, (Patton et al, 2011)).…”

Section: The Gmpr Reactionmentioning

confidence: 99%

“…Only the human and Escherichia coli genes have been cloned and expressed to verify activity (Andrews and Guest, 1988, Moffat and Mackinnon, 1985, Martinelli et al, 2011, Patton et al, 2011, Li et al, 2006, Zhang et al, 2003, Deng et al, 2002). X-ray crystal structures are available for human GMPR1 and GMPR2 in several complexes: E•GMP (2ble, 2bwg, 2a7r, (Li et al, 2006)), E•IMP (2bzn, (Patton et al, 2011)) and E•IMP•NADH (2c6q, (Patton et al, 2011)). Two structures of B. anthracis GMPR can be found in the PDB (1ypf and 2a1y), but there is no record that this protein has actually been assayed for GMPR activity.…”

Section: The Gmpr Reactionmentioning

confidence: 99%

The dynamic determinants of reaction specificity in the IMPDH/GMPR family of (β/α)₈barrel enzymes

Hedstrom

2012

Critical Reviews in Biochemistry and Molecular Biology

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The IMPDH/GMPR family of (β/α)8 enzymes presents an excellent opportunity to investigate how subtle changes in enzyme structure change reaction specificity. IMP dehydrogenase (IMPDH) and GMP reductase (GMPR) bind the same ligands with similar affinities and share a common set of catalytic residues. Both enzymes catalyze a hydride transfer reaction involving a nicotinamide cofactor hydride, and both reactions proceed via the same covalent intermediate. In the case of IMPDH, this intermediate reacts with water while in GMPR it reacts with ammonia. In both cases, the two chemical transformations are separated by a conformational change. In IMPDH, the conformational change involves a mobile protein flap while in GMPR the cofactor moves. Thus reaction specificity is controlled by differences in dynamics, which in turn are controlled by residues outside the active site. These findings have some intriguing implications for the evolution of the IMPDH/GMPR family.

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Crystal Structure of Human Guanosine Monophosphate Reductase 2 (GMPR2) in Complex with GMP

Cited by 28 publications

References 33 publications

Structural insights of a hormone sensitive lipase homologue Est22

Structural insights of a hormone sensitive lipase homologue Est22

Identification of differentially expressed genes in parasitic phase Miamiensis avidus (Ciliophora: Scuticociliatia) using suppression subtractive hybridization

The dynamic determinants of reaction specificity in the IMPDH/GMPR family of (β/α)₈barrel enzymes

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Crystal Structure of Human Guanosine Monophosphate Reductase 2 (GMPR2) in Complex with GMP

Cited by 28 publications

References 33 publications

Structural insights of a hormone sensitive lipase homologue Est22

Structural insights of a hormone sensitive lipase homologue Est22

Identification of differentially expressed genes in parasitic phase Miamiensis avidus (Ciliophora: Scuticociliatia) using suppression subtractive hybridization

The dynamic determinants of reaction specificity in the IMPDH/GMPR family of (β/α)8barrel enzymes

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The dynamic determinants of reaction specificity in the IMPDH/GMPR family of (β/α)₈barrel enzymes