4kxd

Crystal structure of human aminopeptidase A complexed with glutamate and calcium

spinqualitylabelsall models 4kxd, resolution 2.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4kxd is a 1 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 2.15Å Ligands: CA, GLU, NAG, PRD_900017, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function AMPE_HUMAN Appears to have a role in the catabolic pathway of the renin-angiotensin system. Probably plays a role in regulating growth and differentiation of early B-lineage cells. Publication Abstract from PubMed Hypertension is regulated through both the central and systemic renin-angiotensin systems. In the central renin-angiotensin system, zinc-dependent aminopeptidase A (APA) up-regulates blood pressure by specifically cleaving the N-terminal aspartate, but not the adjacent arginine, from angiotensin II, a process facilitated by calcium. Here, we determined the crystal structures of human APA and its complexes with different ligands and identified a calcium-binding site in the S1 pocket of APA. Without calcium, the S1 pocket can bind both acidic and basic residues through formation of salt bridges with the charged side chains. In the presence of calcium, the binding of acidic residues is enhanced as they ligate the cation, whereas the binding of basic residues is no longer favorable due to charge repulsion. Of the peptidomimetic inhibitors of APA, amastatin has higher potency than bestatin by fitting better in the S1 pocket and interacting additionally with the S3' subsite. These results explain the calcium-modulated substrate specificity of APA in central hypertension regulation and can guide the design and development of brain-targeting antihypertensive APA inhibitors. Structural insights into central hypertension regulation by human aminopeptidase a.,Yang Y, Liu C, Lin YL, Li F J Biol Chem. 2013 Aug 30;288(35):25638-45. doi: 10.1074/jbc.M113.494955. Epub, 2013 Jul 25. PMID:23888046 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aminopeptidase 3D structures

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