1ITU

HUMAN RENAL DIPEPTIDASE COMPLEXED WITH CILASTATIN

Summary for 1ITU

• Entry DOI: 10.2210/pdb1itu/pdb
• Related: 1ITQ
• Descriptor: RENAL DIPEPTIDASE, 2-acetamido-2-deoxy-beta-D-glucopyranose, ZINC ION, ... (5 entities in total)
• Functional Keywords: dipeptidase, glycoprotein, membrane-bound, zinc protease beta-lactamase, cilastatin, complex (hydrolase-inhibitor), hydrolase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 84079.76

Authors

Nitanai, Y.,Satow, Y.,Adachi, H.,Tsujimoto, M. (deposition date: 2002-02-03, release date: 2002-08-28, Last modification date: 2024-11-13)

Primary citation

Nitanai, Y.,Satow, Y.,Adachi, H.,Tsujimoto, M.
Crystal Structure of Human Renal Dipeptidase Involved in beta-Lactam Hydrolysis
J.Mol.Biol., 321:177-184, 2002

PubMed 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.

PubMed: 12144777
DOI: 10.1016/S0022-2836(02)00632-0

Experimental method

X-RAY DIFFRACTION (2 Å)