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Crystal structure of human renal dipeptidase involved in beta-lactam hydrolysis.

Nitanai Y, Satow Y, Adachi H, Tsujimoto M
J Mol Biol 321 177-84 (2002)
Cited: 24 times
EuropePMC logo PMID: 12144777

Abstract

Human renal dipeptidase is a membrane-bound glycoprotein hydrolyzing dipeptides and is involved in hydrolytic metabolism of penem and carbapenem beta-lactam antibiotics. The crystal structures of the saccharide-trimmed enzyme are determined as unliganded and inhibitor-liganded forms. They are informative for designing new antibiotics that are not hydrolyzed by this enzyme. The active site in each of the (alpha/beta)(8) barrel subunits of the homodimeric molecule is composed of binuclear zinc ions bridged by the Glu125 side-chain located at the bottom of the barrel, and it faces toward the microvillar membrane of a kidney tubule. A dipeptidyl moiety of the therapeutically used cilastatin inhibitor is fully accommodated in the active-site pocket, which is small enough for precise recognition of dipeptide substrates. The barrel and active-site architectures utilizing catalytic metal ions exhibit unexpected similarities to those of the murine adenosine deaminase and the catalytic domain of the bacterial urease.

Reviews - 1itq mentioned but not cited (1)

  1. Effects of Glycosylation on the Enzymatic Activity and Mechanisms of Proteases. Goettig P. Int J Mol Sci 17 E1969 (2016)

Articles - 1itq mentioned but not cited (3)

  1. A combined computational strategy of sequence and structural analysis predicts the existence of a functional eicosanoid pathway in Drosophila melanogaster. Scarpati M, Qi Y, Govind S, Govind S, Singh S. PLoS One 14 e0211897 (2019)
  2. Structure, mechanism, and substrate profile for Sco3058: the closest bacterial homologue to human renal dipeptidase . Cummings JA, Nguyen TT, Fedorov AA, Kolb P, Xu C, Fedorov EV, Shoichet BK, Barondeau DP, Almo SC, Raushel FM. Biochemistry 49 611-622 (2010)
  3. Evolutionary expansion of the amidohydrolase superfamily in bacteria in response to the synthetic compounds molinate and diuron. Sugrue E, Fraser NJ, Hopkins DH, Carr PD, Khurana JL, Oakeshott JG, Scott C, Jackson CJ. Appl Environ Microbiol 81 2612-2624 (2015)


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  1. Inborn errors in the metabolism of glutathione. Ristoff E, Larsson A. Orphanet J Rare Dis 2 16 (2007)
  2. Peptidase inhibitors in the MEROPS database. Rawlings ND. Biochimie 92 1463-1483 (2010)
  3. Glutathione Degradation. Bachhawat AK, Kaur A. Antioxid Redox Signal 27 1200-1216 (2017)
  4. The enzymology of human eicosanoid pathways: the lipoxygenase branches. Biringer RG. Mol Biol Rep 47 7189-7207 (2020)

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  1. The MEROPS batch BLAST: a tool to detect peptidases and their non-peptidase homologues in a genome. Rawlings ND, Morton FR. Biochimie 90 243-259 (2008)
  2. Similar active sites in lysostaphins and D-Ala-D-Ala metallopeptidases. Bochtler M, Odintsov SG, Marcyjaniak M, Sabala I. Protein Sci 13 854-861 (2004)
  3. N-Acetyl-D-glucosamine-6-phosphate deacetylase: substrate activation via a single divalent metal ion. Hall RS, Xiang DF, Xu C, Raushel FM. Biochemistry 46 7942-7952 (2007)
  4. Metal preferences of zinc-binding motif on metalloproteases. Fukasawa KM, Hata T, Ono Y, Hirose J. J Amino Acids 2011 574816 (2011)
  5. The crystal structure of a novel, latent dihydroorotase from Aquifex aeolicus at 1.7A resolution. Martin PD, Purcarea C, Zhang P, Vaishnav A, Sadecki S, Guy-Evans HI, Evans DR, Edwards BF. J Mol Biol 348 535-547 (2005)
  6. Dipeptidase-1 governs renal inflammation during ischemia reperfusion injury. Lau A, Rahn JJ, Chappellaz M, Chung H, Benediktsson H, Bihan D, von Mässenhausen A, Linkermann A, Jenne CN, Robbins SM, Senger DL, Lewis IA, Chun J, Muruve DA. Sci Adv 8 eabm0142 (2022)
  7. Engineering of cysteine residues leads to improved production of a human dipeptidase enzyme in E. coli. O'Dwyer R, Razzaque R, Hu X, Hollingshead SK, Wall JG. Appl Biochem Biotechnol 159 178-190 (2009)
  8. Purification of human beta2-adrenergic receptor expressed in methylotrophic yeast Pichia pastoris. Noguchi S, Satow Y. J Biochem 140 799-804 (2006)
  9. Hydrolysis of S-aryl-cysteinylglycine conjugates catalyzed by porcine kidney cortex membrane dipeptidase. Poon JC, Josephy PD. Xenobiotica 42 1178-1186 (2012)
  10. Characteristics of a new enantioselective thermostable dipeptidase from Brevibacillus borstelensis BCS-1 and its application to synthesis of a D-amino-acid-containing dipeptide. Baek DH, Song JJ, Kwon SJ, Park C, Jung CM, Sung MH. Appl Environ Microbiol 70 1570-1575 (2004)
  11. A substrate variant as a high-affinity, reversible inhibitor: insight from the X-ray structure of cilastatin bound to membrane dipeptidase. Smyth TP, Wall JG, Nitanai Y. Bioorg Med Chem 11 991-998 (2003)
  12. DPEP1 Balance GSH Involve in Cadmium Stress Response in Blood Clam Tegillarca granosa. Song D, Lin Z, Yuan Y, Qian G, Li C, Bao Y. Front Physiol 9 964 (2018)
  13. A novel lipid metabolism gene signature for clear cell renal cell carcinoma using integrated bioinformatics analysis. Li K, Zhu Y, Cheng J, Li A, Liu Y, Yang X, Huang H, Peng Z, Xu H. Front Cell Dev Biol 11 1078759 (2023)
  14. Application of representational difference analysis to identify genomic differences between Bradyrhizobium elkanii and B. Japonicum species. Soares RA, Passaglia LM. Braz J Microbiol 41 1142-1151 (2010)
  15. Genetic studies of paired metabolomes reveal enzymatic and transport processes at the interface of plasma and urine. Schlosser P, Scherer N, Grundner-Culemann F, Monteiro-Martins S, Haug S, Steinbrenner I, Uluvar B, Wuttke M, Cheng Y, Ekici AB, Gyimesi G, Karoly ED, Kotsis F, Mielke J, Gomez MF, Yu B, Grams ME, Coresh J, Boerwinkle E, Köttgen M, Kronenberg F, Meiselbach H, Mohney RP, Akilesh S, GCKD Investigators, Schmidts M, Hediger MA, Schultheiss UT, Eckardt KU, Oefner PJ, Sekula P, Li Y, Köttgen A. Nat Genet 55 995-1008 (2023)
  16. PvdM of fluorescent pseudomonads is required for the oxidation of ferribactin by PvdP in periplasmic pyoverdine maturation. Sugue MF, Burdur AN, Ringel MT, Dräger G, Brüser T. J Biol Chem 298 102201 (2022)


Related citations provided by authors (1)

  1. Crystallization and preliminary X-ray investigation of a glycoprotein, human renal dipeptidase. Nitanai Y, Satow Y, Adachi H, Tsujimoto M J Cryst Growth 168 280-283 (1996)

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