4ER1

THE ACTIVE SITE OF ASPARTIC PROTEINASES

Summary for 4ER1

• Entry DOI: 10.2210/pdb4er1/pdb
• Related PRD ID: PRD_000382
• Descriptor: ENDOTHIAPEPSIN, N-[(1R,2R,4R)-1-(cyclohexylmethyl)-2-hydroxy-6-methyl-4-{[(2R)-2-methylbutyl]carbamoyl}heptyl]-3-(1H-imidazol-3-ium-4-y l)-N~2~-[3-naphthalen-1-yl-2-(naphthalen-1-ylmethyl)propanoyl]-L-alaninamide (3 entities in total)
• Functional Keywords: acid proteinase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Cryphonectria parasitica (chestnut blight fungus)
• Total number of polymer chains: 1
• Total formula weight: 34628.97

Authors

Quail, J.W.,Cooper, J.B.,Szelke, M.,Blundell, T.L. (deposition date: 1990-10-14, release date: 1991-01-15, Last modification date: 2024-11-20)

Primary citation

Pearl, L.,Blundell, T.
The active site of aspartic proteinases
FEBS Lett., 174:96-101, 1984

PubMed Abstract: The active site of the aspartic proteinase, endothiapepsin, has been defined by X-ray analysis and restrained least-squares refinement at 2.1 A resolution with a crystallographic agreement value of 0.16. The environments of the two catalytically important aspartyl groups are remarkably similar and the contributions of the NH2- and COOH-terminal domains to the catalytic centre are related by a local 2-fold axis. The carboxylates of the aspartyls share a hydrogen bond and have equivalent contacts to a bound water molecule or hydroxonium ion lying on the local diad. The main chains around 32 and 215 are connected by a novel interaction involving diad-related threonines. It is suggested that the two pKa values of the active site aspartyls arise from a structure not unlike that in maleic acid with a hydrogen-bonded intermediate species and a dicarboxylate characterised by electrostatic repulsions between the two negatively charged groups.

PubMed: 6381096
DOI: 10.1016/0014-5793(84)81085-6

Experimental method

X-RAY DIFFRACTION (2 Å)