We show that the only monic orthogonal polynomials $\{P_n\}_{n=0}^{\infty}$ that satisfy $$��(x)\mathcal{D}_{q}^2P_{n}(x)=\sum_{j=-2}^{2}a_{n,n+j}P_{n+j}(x),\; x=\cos��,\;~ a_{n,n-2}\neq 0,~ n=2,3,\dots,$$ where $��(x)$ is a polynomial of degree at most $4$ and $\mathcal{D}_{q}$ is the Askey-Wilson operator, are Askey-Wilson polynomials and their special or limiting cases. This completes and proves a conjecture by Ismail concerning a structure relation satisfied by Askey-Wilson polynomials. We use the structure relation to derive upper bounds for the smallest zero and lower bounds for the largest zero of Askey-Wilson polynomials and their special cases.