How to replace the last (and only last) character in a string?

[Johny]

Let's suppose
s='12345 4343 454'
How can I replace the last '4' character?
I tried
string.replace(s,s[len(s)-1],'r')
where 'r' should replace  the last '4'.
But it doesn't work.
Can anyone explain why?

Thanks
L.