POTASSIUM-DEPENDENT MOLECULES 201
details in the discussion of Ca 2+ - ATPase, Section 6.4.2.) An informative ribbon
display of the PDB: 1Q3I Na + /K + - ATPase molecule is found in the http://www.
patbase.kvl.dk/ website, click on “ Crystal Structures of P - Type ATPases. ” The
same diagram and others are found in Figure 2 of reference 13. Figure 3 of
the same reference shows the primary and secondary structure alignment of
the pig Na + /K + - ATPase with the rabbit sarcoplasmic reticulum Ca 2+ - ATPase
N - domain discussed in Section 6.4.2.
The PDB: 1Q3I Na + /K + - ATPase N - domain fold is described as a seven -
stranded antiparallel β - sheet with an additional hairpin consisting of two β -
strands. Five α - helices of varying lengths and connecting loops complete the
secondary structure. Several important motifs are conserved when the Na + /K + -
ATPase N - domain is compared to that of Ca 2+ - ATPase (PDB: 1EUL; see
Section 6.4.2). Many of these motifs, conserved in most P - type ATPases, are
important in forming the ATP - binding pocket, and many residues within these
motifs are involved in ATP hydrophobic and electrostatic binding. First, in the
β 1 strand, residues met379, val381, and met384 are conserved in both Na + /K + -
ATPase and Ca 2+ - ATPase (the Na + /K + - ATPase numbering system for PDB:
1Q3I is used here). These hydrophobic residues are mostly directed away from
the enzyme ’ s surface. The second patch of conserved residues in α - helix 1
include leu414, ile417, and leu420. These residues pack against the beta strands
β 4, β 5, β 6, and β 7. The conserved asn422 residue, near the C - terminal end of
α - helix 1, hydrogen bonds to the likewise conserved arg464 side chain. The
arg464 NH1 bonding distance to asn422 ’ s main chain O equals 3.3 Å ). At the
beginning ofα - helix 2, the hydrophilic residues asp(glu)443, ser(thr)445, and
glu446 are conserved (residues in parentheses are those found in Ca 2+ - ATPase).
These comprise the so - called DASE (or GD/(E)AS/(T)E) motif found in many
P - type ATPases. Unfortunately, Na + /K + - ATPase residues phe475 through
lys480 are disordered in the PDB: 1Q3I structure. It would be helpful to be
able to visualize this region because it contains a conserved and essential phe-
nylalanine residue that is invoked in many other ATPase structures in forming
π – π interactions with the adenine ring of ATP. A highly conserved aa sequence,
comprised of residues lys501, gly502, ala503, pro504, and glu505 (the so - called
KGAPE motif), is located at the end of strand β 5 carrying on through the
beginning of shortα - helix 4. In other N - domain structures, lys501 interacts
directly with ATP. Finally, β 6 carries the motif RXL, with residues arg544 and
leu546 defi ning the surface of the ATP - binding pocket. Despite several attempts,
the reference 13 author found that nucleotides did not bind to the Na + /K + -
ATPase N - domain described here; however, a possible ATP binding scheme
agrees with that found in other P - type ATPases (see discussion for Ca 2+ -
ATPase found in Section 6.4.2). A hydrophobic binding site around leu546 has
a suitable size to accommodate ATP ’ s adenine ring, a hydrophilic site near the
N - terminal end of α - helix 2 is suitable to interact with its ribose ring, and a
positively charged site at arg544 may interact with the phosphate chain.
The reference 13 author compared the N - domain Na + /K + - ATPase X - ray
crystallographic structure with NMR solution structures also published in 2003