3mdj

ER Aminopeptidase, ERAP1, Bound to the Zinc Aminopeptidase Inhibitor, Bestatin

spinqualitylabelsall models 3mdj, resolution 2.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3mdj is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.95Å Ligands: BES, BMA, MAN, NAG, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ERAP1_HUMAN Aminopeptidase that plays a central role in peptide trimming, a step required for the generation of most HLA class I-binding peptides. Peptide trimming is essential to customize longer precursor peptides to fit them to the correct length required for presentation on MHC class I molecules. Strongly prefers substrates 9-16 residues long. Rapidly degrades 13-mer to a 9-mer and then stops. Preferentially hydrolyzes the residue Leu and peptides with a hydrophobic C-terminus, while it has weak activity toward peptides with charged C-terminus. May play a role in the inactivation of peptide hormones. May be involved in the regulation of blood pressure through the inactivation of angiotensin II and/or the generation of bradykinin in the kidney. Publication Abstract from PubMed ERAP1 trims antigen precursors to fit into MHC class I proteins. To fulfill this function, ERAP1 has unique substrate preferences, trimming long peptides but sparing shorter ones. To identify the structural basis for ERAP1's unusual properties, we determined the X-ray crystal structure of human ERAP1 bound to bestatin. The structure reveals an open conformation with a large interior compartment. An extended groove originating from the enzyme's catalytic center can accommodate long peptides and has features that explain ERAP1's broad specificity for antigenic peptide precursors. Structural and biochemical analyses suggest a mechanism for ERAP1's length-dependent trimming activity, whereby binding of long rather than short substrates induces a conformational change with reorientation of a key catalytic residue toward the active site. ERAP1's unique structural elements suggest how a generic aminopeptidase structure has been adapted for the specialized function of trimming antigenic precursors. Structural basis for antigenic peptide precursor processing by the endoplasmic reticulum aminopeptidase ERAP1.,Nguyen TT, Chang SC, Evnouchidou I, York IA, Zikos C, Rock KL, Goldberg AL, Stratikos E, Stern LJ Nat Struct Mol Biol. 2011 May;18(5):604-13. Epub 2011 Apr 10. PMID:21478864 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aminopeptidase 3D structures

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