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==New Delhi Metallo-Beta-Lactamase==  
==Karyopherin Beta 2==  
The New Delhi metallo-beta-lactamse <scene name='37/372723/Chain_a_4eyl/1'>(NDM-1)</scene> in complex with meropenem demonstrates the mechanism in which the active site binds and hydrolyzes the carbapenem, in this case meropenem.  
Karyopherinβ is a group of proteins that is composed of both importins and exportins. Importins are proteins that carry cargos into the nucleus while exportins serve the opposite function. As of today, twenty different Kapβs have been identified. Each of these Kapβs is capable of recognizing and transporting a specific group of cargos. In order to bind to its cargo a Kapβ has to recognize a Nuclear Localization or Export Signal (NLS or NES).
Zn1, coordinated by three histidine residues, acts as a major constituent of oxyanion hole to stabilize tetrahedral intermediate. It also acts as a Lewis acid for interaction with lactam carbonyl in Michaelis complex. Zn1 also acts to suppress the pka of the hydrolytic water to (~5-6) to facilitate it's nucleophillic role.  
<Structure load='4eyl' size='350' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene NDM1' />


The NDM-1 is a metallo-protein and associated with the bacterial cell membrane. The active site contains key features for hydrolyzing carbapenems:
Karyopherin beta 2 (kapβ2) is an importin that transports various cargo protein into the nucleus through interactions :with nucleoporins,  which are proteins of the nucleopore complex (NPC). One might overlook the significance of this :protein but actually plays a crucial role in the human body by mediating transport of RNA- binding proteins involved in :transcription, RNA processing, RNA transport and translation. The structure of KAPβ is composed of 20 antiparallel helices :called HEAT repeats. These HEAT repeats contribute to kapβ2’s large superhelical shape. That form two arches: one at the :N-terminal and the other at the C- terminal. Through recognition of a nuclear localization signal (NLS) located on its :cargo, kapβ2 binds to its cargo via its C-terminal arch. Release of the cargo is mediated by RanGTP, which once bound, :modifies the shape of kapβ2.  Release of the cargo is mediated once contact occurs between RanGTP and N-terminal arch of :Kapβ2.
*Zinc ion 1(Zn1) is coordinated by three histidine residues: H120, H122 and H189
*Zinc ion (Zn2) is coordinated by three residues: H250, C208 and D124


 
 

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Wayne Decatur, Student, Allison Granberry, Marisa L. VanBrakle