Počet záznamů: 1

Structural and Biochemical Characterization of a Novel Aminopeptidase from Human Intestine

SYSNO ASEP	0444448
Druh ASEP	J - Článek v odborném periodiku
Zařazení RIV	J - Článek v odborném periodiku
Poddruh J	Článek ve WOS
Název	Structural and Biochemical Characterization of a Novel Aminopeptidase from Human Intestine
Tvůrce(i)	Tykvart, Jan (UOCHB-X)_{RID, ORCID} Bařinka, Cyril (BTO-N)_{RID, ORCID} Svoboda, Michal (UOCHB-X)_RID Navrátil, Václav (UOCHB-X)_{RID, ORCID} Souček, Radko (UOCHB-X) Hubálek, Martin (UOCHB-X)_{RID, ORCID} Hradilek, Martin (UOCHB-X)_ORCID Šácha, Pavel (UOCHB-X)_{RID, ORCID} Lubkowski, J. (US) Konvalinka, Jan (UOCHB-X)_{RID, ORCID}
Celkový počet autorů	10
Zdroj.dok.	Journal of Biological Chemistry. - : Elsevier - ISSN 0021-9258 Roč. 290, č. 18 (2015), s. 11321-11336
Poč.str.	16 s.
Jazyk dok.	eng - angličtina
Země vyd.	US - Spojené státy americké
Klíč. slova	glutamate carboxypeptidase II ; reaction mechanism ; expression
Vědní obor RIV	CE - Biochemie
CEP	GAP304/12/0847 GA ČR - Grantová agentura ČR
	LO1302 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy
	ED1.1.00/02.0109 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy
Institucionální podpora	UOCHB-X - RVO:61388963 ; BTO-N - RVO:86652036
UT WOS	000353719400010
EID SCOPUS	84929460052
DOI	10.1074/jbc.M114.628149
Anotace	N-acetylated alpha-linked acidic dipeptidase-like protein (NAALADase L), encoded by the NAALADL1 gene, is a close homolog of glutamate carboxypeptidase II, a metallopeptidase that has been intensively studied as a target for imaging and therapy of solid malignancies and neuropathologies. However, neither the physiological functions nor structural features of NAALADase L are known at present. Here, we report a thorough characterization of the protein product of the human NAALADL1 gene, including heterologous overexpression and purification, structural and biochemical characterization, and analysis of its expression profile. By solving the NAALADase L x-ray structure, we provide the first experimental evidence that it is a zinc-dependent metallopeptidase with a catalytic mechanism similar to that of glutamate carboxypeptidase II yet distinct substrate specificity. Aproteome-based assay revealed that the NAALADL1 gene product possesses previously unrecognized aminopeptidase activity but no carboxy-or endopeptidase activity. These findings were corroborated by site-directed mutagenesis and identification of bestatin as a potent inhibitor of the enzyme. Analysis of NAALADL1 gene expression at both the mRNA and protein levels revealed the small intestine as the major site of protein expression and points toward extensive alternative splicing of the NAALADL1 gene transcript. Taken together, our data imply that the NAALADL1 gene product's primary physiological function is associated with the final stages of protein/peptide digestion and absorption in the human digestive system. Based on these results, we suggest a new name for this enzyme: human ileal aminopeptidase (HILAP).
Pracoviště	Ústav organické chemie a biochemie
Kontakt	asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Viktorie Chládková, Tel.: 232 002 434
Rok sběru	2016

Počet záznamů: 1